in a preferred embodiment , compounds of this invention are defined by formula ( i ) wherein , r is selected from the group consisting of : ## str5 ## wherein x 4 is an halogen ( e . g ., cl , br , or f ). y is a linear c 1 - 6 alkyl , phenyl ethyl or phenylmethyl . a is selected from the group consisting of tetrahydro isoquinoline carboxylate ; l or d - pipecolate ; aminocyclohexyl carboxylate ; and β - cyclohexyl alanine . in an alternative preferred embodiment , r is selected from the group consisting of ## str6 ## in a preferred embodiment , the chiral center shown as * in formula ( i ) is in the l configuration . preferred compounds if this invention are defined by formula ( i ) wherein p is defined by formula ( x ): q , if present , is a residue derived from an l - α - amino acid or a cyclic imino acid ; x 3 , if present , is any hydrophobic α - amino acid residue ; r 2 is a hydrophobic oligopeptide having all or a portion of the sequence pro - glu - glu - v - w - x , ( seq . id no : 2 ) where v and w are independently hydrophobic amino acid residues and x is selected from the group consisting of d - glu or l - glu and gln ; and ## str7 ## wherein each r 5 is independently selected from the group consisting of hydrogen , alkyl , aryl , and aralkyl ; with the proviso that p consists of at least 6 amino or imino acid residues . z may preferably comprise an alkyl chain wherein said alkyl chain may be interrupted by one or more atoms of o , s , or n atom , carbonyl or amide group . z preferably consist of at least 15 atoms in lenght comprising at least one ω - amino acid . z preferably consist of at least 15 atoms in lenght comprising at least one α - amino acid . in a further embodiment z preferably consist of at least 15 atoms in lenght comprising a combination of at least one ω - amino acid and at least one α - amino acid . in an alternative preferred embodiment , z is [ nh --( chr 6 ) 1 - 11 -- co ] 1 - 4 , [ nh --( ch 2 ) 1 - 11 -- co ] 1 - 4 or ( nhch 2 ch ═ chch 2 co ) 3 wherein r 6 is an alkyl or any naturally occuring amino acid side chain . most preferably , z is selected from the group consisting of : ( 12 - aminododecanoic acid )- 4 - aminobutyric acid )-; ( 12 - aminododecanoic acid )- 6 - aminocaproic acid ); ( 8 - aminocapylic acid )- 4 - aminobutyric acid )-; ( 11 - aminoundecanoic acid )- glycyl ); ( glycyl )- 12 - aminododecanoic acid ); ( 12 - aminododecanoic acid )- glycyl ); and ( β - alanyl - glycyl - glycyl - 5 - aminovaleric acid ( seq . id no : 3 ). in a preferred embodiment , g and g 1 may independently be : ## str8 ## wherein r 3 is selected from the group consisting of ## str9 ## wherein r 4 is hydrogen or alkyl ; and each r 7 is independently ch 3 or hydrogen . in a further preferred embodiment , g and g 1 may independently be an aspartic acid residue , a glutamic acid residue or a glutamic alkyl ester residue . in a most preferred embodiment , g and g 1 may independently be aspartic or glutamic acid . q is preferably selected from the group consisting of proline residue and glutamic acid residue . x 3 is preferrably ile , leu , allo - ile or tert - butyl alanine . r 2 is a hydrophobic oligopeptide having all or a portion of the sequence pro - glu - glu - v - w - x , ( seq id no : 4 ) where v - w is selected from the group consisting of residue of tyr - leu , tyr - ala , tyr -( β - cyclohexylalanine ), ( β - cyclohexylalanine )- leu , pro - tyr , ala -( β - cyclohexylalanine ), phe - tyr and , ( β - cyclohexylalanine )- ala ; and x is selected from the group consisting of d - glu and gln . in a preferred embodiment , v - w would be selected from the group consisting of tyr - leu , tyr - ala , tyr - cha , cha - leu , and cha - ala . in a further preferred embodiment , the compounds of this invention may be described by formula ( ii ) said formula ( ii ) comprising an active site portion ( as ) and a fibrinogen recognition exosite portion ( p ) linked through a linker ( z ): wherein the ( as ) portion is preferably selected from the group consisting of bzs - arg -( d - pip ); dansyl - arg -( d - pip ); dansyl - arg -( l - pip ); dansyl - nle -( d - pip ); ( d - phe )- arg -( d - pip ); fmoc - arg -( d - pip ); dansyl - arg -( d - tic ); dansyl -( d - arg )-( d - pip ); dansyl - phe -( d - pip ); dansyl - cha -( d - pip ); ( d - cha )- arg -( d - pip ); α - naphthyl sulfonyl - arg -( d - pip ); β - naphthyl sulfonyl - arg -( d - pip ); 4 - tert - butyl - benzene sulfonyl - arg -( d - pip ); dansyl - arg -( d - cha ); dansyl - arg - acha ; phenyl ethyl sulfonyl - arg -( d - pip ); β - dihydroanthracenyl - β - sulfonyl - arg -( d - pip ); (+)- camphorsulfonyl - arg -( d - pip ); ( d - tic )- arg -( d - pip ); 4 - bromobenzenesulfonyl - arg -( d - pip ) and 2 , 4 , 6 triisopropylbenzenesulfonyl - arg -( d - pip ). the ( z ) portion is preferably selected from the group consisting of ( 12 - aminododecanoic acid )- 4 - aminobutyric acid )-; ( 12 - aminododecanoic acid )- 6 - aminocaproic acid ); ( 8 - aminocapylic acid )- 4 - aminobutyric acid )-; ( 12 - aminododecanoic acid ) - asparagyl - glycyl ); ( 4 - aminobutyric acid - glycyl ); ( 5 - amino valeric acid )- glycyl ); ( 6 - aminocaproic acid )- glycyl ); ( 7 - aminoheptanoic acid )- glycyl ); ( 8 - aminocapylic acid )- glycyl ); ( 12 - aminododecanoic acid ); ( 11 - aminoundecanoic acid )- glycyl ); ( glycyl )- 12 - aminododecanoic acid ); ( 12 - aminododecanoic acid )- glycyl ); and ( β - alanyl - glycyl - glycyl - 5 - aminovaleric acid ) ( seq id no : 3 ). the ( p ) portion is preferably selected from the group consisting of asp - phe - glu - glu - ile - pro - glu - glu - tyr - leu - gln - oh ( seq id no : 5 ); asp - tyr - glu - pro - ile - pro - glu - glu - ala -( l - β - cyclohexylalanine )-( d - glu )- oh ( seq id no : 6 ); and asp - phe - glu - pro - ile - pro - tyr - oh ( seq id no : 7 ). the biological activity of most of the compounds of this invention were evaluated by two different biological assays . the first assay is an in vitro assay that evaluates the equilibrium dissociation constant ( k i ) and the inhibitor concentration required to double the time to fibrinogen clot formation ( ic 50 ). the second assay in an in vivo assay that determines both , the dose of the compounds of this invention necessary to double the occlusion time and the dose of the compounds of this invention necessary to achieve patency at 60 min . in a carotid injury - induced thrombosis . as fig . ( 2b ) demonstrates , the compounds of this invention , more specifically , p448 was exposed to three types of proteases : 1 ) thrombin , which forms a complex with the inhibitor and may hydrolyse it , 2 ) plasma proteases encountered by inhibitors during the blood circulation , and 3 ) kidney proteases , which are heavily involved in the clearance of the peptides . the compounds of this invention were very stable to enzyme degradation . the compounds of the present invention show an inhibitory activity comparable to the inhibitory activity of hirudin . for example , table ii demonstrate that p448 , p531 , p532 and p540 have k i values under 0 . 032 nm . table iii demontrates that p527 , p501 , p500 and p513 have k i values under 0 . 027 nm . table iv shows that p535 and p551 have k i values under 0 . 00330 nm . table v shows that bch - 2733 has a k i of 0 . 8 nm . finally table vi demonstrate the activity of the compounds of this invention in a carotid induced thrombosis model in the rat mediated by fecl 3 . for a matter of comparison , two known thrombin inhibitors ; hirulog - 8 ™ and heparin were also tested . hirulog - 8 ™ is a thrombin inhibitor having a peptide sequence similar to the peptide sequence of hirudin . the results indicate that the compounds of this invention are capable of inhibiting occlusion in the rat carotid artery at doses in the order of ≧ 0 . 25 mg / kg i . v . the more preferred compounds of this invention confer full arterial patency at dose as low as 0 . 5 - 1 mg / kg i . v whereas hirulog - 8 ™ which demonstrates patency at 4 mg / kg .. 4 - bromobenzenesulfonyl - arg ( d - pipecolic acid )-( 12 - aminododecanoic acid )- 4 - aminobutyric acid )- asp - phe - glu - pro - ile - pro - tyr - oh ( bch - 2733 )( seq id no : 52 ); and the more preferred compounds of this invention having a k i value smaller then 1 nm are ; ( p448 ); ( p471 );( p531 );( p532 ); ( p552 ); ( p556 );( p540 ); ( p534 ); ( p528 ); ( p527 ); ( p500 ); ( p501 );( p498 ); ( p513 ); ( p535 ); ( p551 ); ( p581 ); ( p553 ); and ( bch - 2733 ). the most preferred compounds of this invention having a k i value smaller then 0 . 1 nm are : ( p448 );( p531 );( p532 ); ( p540 ); ( p552 ); ( p527 ); ( p500 ); ( p501 ); ( p513 ); ( p535 ); ( p551 ); ( p553 ); and ( p581 ). it should be noted that a person skilled in the art could substitute suitable linkers and synthesize variants of such active bivalent hirudin - like inhibitors . several such alternative linker segments were synthesized and were found to be effective . table ii discloses several particularly effective examples . in addition to the species discussed supra some other preferred linkers are ava - glycine , glycine - ada , ada - glycine , bal - glycine - glycine - ava ( seq id no : 54 ). it should be noted that the bivalent inhibitor sequences exemplified in table iii all use the natural hirudin exosite . while it may be possible that , for use in therapy , a compound of the invention may be administered as the raw chemical , it is preferable to present the active ingredient as a pharmaceutical formulation . it will be appreciated by those skilled in the art that the compounds of formula ( i ) contain at least one chiral centre ( shown as * in formula i ) and thus exist in the form of two enantiomers and mixtures thereof . all such enantiomers and mixtures thereof are included within the scope of the invention . it will be appreciated by those skilled in the art that the compounds of formula ( i ) or ( ii ) may be modified to provide pharmaceutically acceptable salts thereof which are included within the scope of the invention . pharmaceutically acceptable salts of the compounds of formula ( i ) or ( ii ) include those derived from pharmaceutically acceptable inorganic and organic acids and bases . examples of suitable acids include hydrochloric , hydrobromic , sulphuric , nitric , perchloric , fumaric , maleic , phosphoric , glycollic , lactic , salicylic , succinic , toluene - p - sulphonic , tartaric , acetic , citric , methanesulphonic , formic , benzoic , malonic , naphthalene - 2 - sulphonic and benzenesulphonic acids . other acids such as oxalic , while not in themselves pharmaceutically acceptable , may be useful as intermediates in obtaining the compounds of the invention and their pharmaceutically acceptable acid addition salts . the invention thus further provides a pharmaceutical formulation comprising a compound of formula ( i ) and ( ii ) and pharmaceutically acceptable acid addition salt thereof together with one or more pharmaceutically acceptable carriers therefor and , optionally , other therapeutic and / or prophylactic ingredients . the carrier ( s ) must be &# 34 ; acceptable &# 34 ; in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof . in a further embodiment of the present invention is provided the use of a compounds of formula ( i ) and ( ii ) or a pharmaceutically acceptable salt in the manufacture of a medicament for the treatment of vascular disease in a mammal including human . in an alternative aspect of the present invention is provided a method for the treatment of vascular disease for the treatment of a mammal , including human comprising the administration of an effective amount of a compound of formula ( i ) or ( ii ). it will be appreciated by people skilled in the art that treatment extends to prophylaxis as well to the treatment of established vascular disease . the compounds of the present invention are useful in combinations , formulations and methods for the treatment and prophylaxis of vascular diseases . these diseases include myocardial infarction , stroke , pulmonary embolism , deep vein thrombosis , peripheral arterial occlusion , restenosis following arterial injury or invasive cardiological procedures , acute or chronic atherosclerosis , edema and inflammation , cancer and metastasis . the term &# 34 ; combination &# 34 ; as used herein , includes a single dosage form containing at least one compound of this invention and at least one thrombolytic agent , a multiple dosage form , wherein the thrombin inhibitor and the thrombolytic agent are administered separately , but concurrently , or a multiple dosage form wherein the two components are administered separately , but sequentially . in sequential administration , the thrombin inhibitor may be given to the patient during the time period ranging from about 5 hours prior to about 5 hours after administration of the thrombolytic agent . preferably , the thrombin inhibitor is administered to the patient during the period ranging from 2 hours prior to 2 hours following administration of the thrombolytic agent . in these combinations , the thrombin inhibitor and the thrombolytic agent work in a complementary fashion to dissolve blood clots , resulting in decreased reperfusion times and increased reocclusion times in patients treated with them . specifically , the thrombolytic agent dissolves the clot , while the thrombin inhibitor prevents newly exposed , clot - entrapped or clot - bound thrombin from regenerating the clot . the use of the thrombin inhibitor in the formulations of this invention advantageously allows the administration of a thrombolytic reagent in dosages previously considered too low to result in thrombolytic effects if given alone . this avoids some of the undesirable side effects associated with the use of thrombolytic agents , such as bleeding complications . thrombolytic agents which may be employed in the combinations of the present invention are those known in the art . such agents include , but are not limited to , tissue plasminogen activator purified from natural sources , recombinant tissue plasminogen activator , streptokinase , urokinase , purokinase , anisolated streptokinase plasminogen activator complex ( aspac ), animal salivary gland plasminogen activators and known , biologically active derivatives of any of the above . various dosage forms may be employed to administer the formulations and combinations of this invention . these include , but are not limited to , parenteral administration , oral administration and topical application . the formulations and combinations of this invention may be administered to the patient in any pharmaceutically acceptable dosage form , including those which may be administered to a patient intravenously as bolus or by continued infusion , intramuscularly -- including paravertebrally and periarticularly -- subcutaneously , intracutaneously , intra - articularly , intrasynovially , intrathecally , intra - lesionally , periostally or by oral , nasal , or topical routes . such compositions and combinations are preferably adapted for topical , nasal , oral and parenteral administration , but , most preferably , are formulated for parenteral administration . parenteral compositions are most preferably administered intravenously either in a bolus form or as a constant infusion . for parenteral administration , fluid unit dose forms are prepared which contain the compounds of the present invention and a sterile vehicle . the compounds of this invention may be either suspended or dissolved , depending on the nature of the vehicle and the nature of the particular compounds of this invention . parenteral compositions are normally prepared by dissolving the compounds of this invention in a vehicle , optionally together with other components , and filter sterilizing before filling into a suitable vial or ampule and sealing . preferably , adjuvants such as a local anesthetic , preservatives and buffering agents are also dissolved in the vehicle . the composition may then be frozen and lyophilized to enhance stability . parenteral suspensions are prepared in substantially the same manner , except that the active component is suspended rather than dissolved in the vehicle . sterilization of the compositions is preferably achieved by exposure to ethylene oxide before suspension in the sterile vehicle . advantageously , a surfactant or wetting agent is included in the composition to facilitate uniform distribution of its components . tablets and capsules for oral administration may contain conventional excipients , such as binding agents , fillers , diluents , tableting agents , lubricants , disintegrants , and wetting agents . the tablet may be coated according to methods well known in the art . suitable fillers which may be employed include cellulose , mannitol , lactose and other similar agents . suitable disintegrants include , but are not limited to , starch , polyvinylpyrrolidone and starch derivatives , such as sodium starch glycolate . suitable lubricants include , for example , magnesium stearate . suitable wetting agents include sodium lauryl sulfate . oral liquid preparations may be in the form of aqueous or oily suspensions , solutions , emulsions , syrups or elixirs , or may be presented as a dry product for reconstitution with water or another suitable vehicle before use . such liquid preparations may contain conventional additives . these include suspending agents , such as sorbitol , syrup , methyl cellulose , gelatin , hydroxyethylcellulose , carboxymethylcellulose , aluminum stearate gel or hydrogenated edible fats , emulsifying agents which include lecithin , sorbitan monooleate , polyethylene glycols , or acacia , non - aqueous vehicles , such as almond oil , fractionated coconut oil , and oily esters , and preservatives , such as methyl or propyl p - hydroxybenzoate or sorbic acid . formulations for topical administration may , for example , be in aqueous jelly , oily suspension or emulsified ointment form . the dosage and dose rate of the compounds of this invention will depend on a variety of factors , such as the weight of the patient , the specific pharmaceutical composition used , the object of the treatment , i . e ., therapy or prophylaxis , the nature of the thrombotic disease to be treated , and the judgment of the treating physician . according to the present invention , a preferred pharmaceutically effective daily dose of the compounds of this invention is between about 1 μg / kg body weight of the patient to be treated (&# 34 ; body weight &# 34 ;) and about 5 mg / kg body weight . in combinations containing a thrombolytic agent , a pharmaceutically effective daily dose of the thrombolytic is between about 10 % and 80 % of the conventional dosage range . the &# 34 ; conventional dosage range &# 34 ; of a thrombolytic agent is the daily dosage used when that agent is employed in a monotherapy [ physician &# 39 ; s desk reference 1989 , 43rd edition , edward r . barnhart , publisher ]. that conventional dosage range will , of course , vary depending on the thrombolytic agent employed . examples of conventional dosage ranges are as follows : urokinase -- 500 , 000 to 6 , 250 , 000 units / patient , streptokinase -- 140 , 000 to 2 , 500 , 000 units / patient , tpa -- 0 . 5 to 5 . 0 mg / kg body weight , aspac -- 0 . 1 to 10 units / kg body weight . most preferably , the therapeutic and prophylactic compositions of the present invention comprise a dosage of between about 10 μg / kg body weight and about 500 μg / kg body weight of the compounds of this invention . most preferred combinations comprise the same amount of the compounds of this invention and between about 10 % and about 70 % of the conventional dosage range of a thrombolytic agent . it should also be understood that a daily pharmaceutically effective dose of either the compounds of this invention or the thrombolytic agent present in combinations of the invention , may be less than or greater than the specific ranges cited above . once improvement in the patient &# 39 ; s condition has occurred , a maintenance dose of a combination or composition of this invention is administered , if necessary . subsequently , the dosage or the frequency of administration , or both , may be reduced , as a function of the symptoms , to a level at which the improved condition is retained . when the symptoms have been alleviated to the desired level , treatment should cease . patients may , however , require intermittent treatment upon any recurrence of disease symptoms . according to an alternate embodiment of this invention , compounds may be used in compositions and methods for coating the surfaces of invasive devices , resulting in a lower risk of clot formation or platelet activation in patients receiving such devices . surfaces that may be coated with the compositions of this invention include , for example , prostheses , artificial valves , vascular grafts , stents and catheters . methods and compositions for coating these devices are known to those of skill in the art . these include chemical cross - linking or physical adsorption of the compounds of this invention - containing compositions to the surfaces of the devices . according to a further embodiment of the present invention , compounds may be used for ex vivo thrombus imaging in a patient . in this embodiment , the compounds of this invention are labelled with a radioisotope . the choice of radioisotope is based upon a number of well - known factors , for example , toxicity , biological half - life and detectability . preferred radioisotopes include , but are not limited to 125 i , 123 i and 111 i . techniques for labelling the compounds of this invention are well known in the art . most preferably , the radioisotope is 123 i and the labelling is achieved using 123 i - bolton - hunter reagent . the labelled thrombininhibitor is administered to a patient and allowed to bind to the thrombin contained in a clot . the clot is then observed by utilizing well - known detecting means , such as a camera capable of detecting radioactivity coupled to a computer imaging system . this technique also yields images of platelet - bound thrombin and meizothrombin . this invention also relates to compositions containing the compounds of this invention and methods for using such compositions in the treatment of tumor metastases . the efficacy of the compounds of this invention for the treatment of tumor metastases is manifested by the inhibition inhibitors to inhibit thrombin - induced endothelial cell activation . this inhibition includes the repression of platelet activation factor ( paf ) synthesis by endothelial cells . these compositions and methods have important applications in the treatment of diseases characterized by thrombin - induced inflammation and edema , which is thought to be mediated be paf . such diseases include , but are not limited to , adult respiratory distress syndrome , septic shock , septicemia and reperfusion damage . early stages of septic shock include discrete , acute inflammatory and coagulopathic responses . it has previously been shown that injection of baboons with a lethal dose of live e . coli leads to marked declines in neutrophil count , blood pressure and hematocrit . changes in blood pressure and hematocrit are due in part to the generation of a disseminated intravascular coagulopathy ( dic ) and have been shown to parallel consumption of fibrinogen [ f . b . taylor et al ., &# 34 ; protein c prevents the coagulopathic and lethal effects of escherichia coli infusion in the baboon &# 34 ;, j . clin . invest ., 79 , pp . 918 - 25 ( 1987 )]. neutropenia is due to the severe inflammatory response caused by septic shock which results in marked increases in tumor necrosis factor levels . the compounds of this invention may be utilized in compositions and methods for treating or preventing dic in septicemia and other diseases . this invention also relates to the use of the above - described compounds , or compositions comprising them , as anticoagulants for extracorporeal blood . as used herein , the term &# 34 ; extracorporeal blood &# 34 ; includes blood removed in line from a patient , subjected to extracorporeal treatment , and then returned to the patient in such processes as dialysis procedures , blood filtration , or blood bypass during surgery . the term also includes blood products which are stored extracorporeally for eventual administration to a patient and blood collected from a patient to be used for various assays . such products include whole blood , plasma , or any blood fraction in which inhibition of coagulation is desired . the amount or concentration of compounds of this invention in these types of compositions is based on the volume of blood to be treated or , more preferably , its thrombin content . preferably , an effective amount of a compounds of this invention of this invention for preventing coagulation in extracorporeal blood is from about 1 μg / 60 ml of extracorporeal blood to about 5 mg / 60 ml of extracorporeal blood . the compounds of this invention may also be used to inhibit clot - bound thrombin , which is believed to contribute to clot accretion . this is particularly important because commonly used anti - thrombin agents , such as heparin and low molecular weight heparin , are ineffective against clot - bound thrombin . finally , the compounds of this invention may be employed in compositions and methods for treating neurodegenerative diseases . thrombin is known to cause neurite retraction , a process suggestive of the rounding in shape changes of brain cells and implicated in neurodegenerative diseases , such as alzheimer &# 39 ; s disease and parkinson &# 39 ; s disease . in order that the invention described herein may be more fully understood , the following examples are set forth . it should be understood that these examples are for illustrative purposes only and are not to be construed as limiting this invention in any manner . human α - thrombin ( 3 , 000 nih units / mg ), bovine fibrinogen (˜ 70 % of protein , 85 % of protein clottable ), tos - gly - pro - arg - amc . hcl salt , poly ( ethylene glycol ) 8000 ™, ada and tris were purchased from sigma inc . amc dansyl chloride , 1 - naphthalenesulfonyl chloride , 2 - naphthalenesulfonyl chloride , 4 - tert - butylbenzenesulfonyl chloride , ada , ava and d , l - pip were were obtained from aldrich . boc - abu , boc - bal , boc - aca , boc - aha , boc - cha , boc - d - cha , boc - l - pip , boc - d - pip , and boc - d - tic were purchased from bachem . acha was obtained from fluka inc . boc - ada , boc - d , l - pip , and boc - acha were prepared according to the procedure described by chaturvedi , d . n ., knittel , j . j ., hruby , v . j ., castrucci , a . m ., & amp ; hadley , m . e . ( 1984 ) j . med . chem . 27 , 1406 - 1410 which is hereby incorporated by reference . all other amino acid derivatives for peptide synthesis were purchased from advanced chemtech except boc - glu ( obzl )- oh , which was obtained from sigma . the side chain protecting groups for boc - amino acids were benzyl for glutamic acid ( glu ) and aspartic acid ( asp ), tosyl ( tos ) for arginine ( arg ) and 2 - bromobenzyloxycarbonyl for tyrosine ( tyr ). boc - gln - och 2 - phenylacetylamidomethyl resin ( 0 . 714 mmol / g ) and p - methyl - benzhydrylamin resin ( 0 . 770 mmol / g ) were purchased from applied biosystems inc . boc - d - glu ( obzl ()- och2 - pheynylacetylamidomethyl resin ( 0 . 31 mmol / g ) was purchased from peninsula laboratories , inc . the solvents for peptide synthesis were obtained from b & amp ; j chemicals and applied biosystems inc . citric acid was purchased from anachemia . hf and tfa were purchased from matheson and halocarbon products co ., respectively . the peptides were prepared according to the method described in szewczuk , z ., gibbs , b . f ., yue , s .- y ., purisima , e ., & amp ; konishi , y . ( 1992 ) biochemistry 31 , 9132 - 9140 which is hereby incorporated by reference . final products were obtained as lyophilizates with 98 % or higher purity estimated by analytical hplc . the purified peptides were identified by amino acid analysis on a beckman model 6300 ™ high performance analyzer and by molecular mass analysis using a sciex api iii ™ mass spectrometer . peptide contents in lyophilizates were determined by the amino acid analysis . following this procedure , the following peptides were synthesized : p429 , p428 , p431 , p430 , p396 , p448 , p447 , p471 , p472 , p473 , p476 , p477 , p493 , p492 , p531 , p532 , p556 , p552 , p540 , p534 , p482 , p482 , p483 , p484 , p514 , p526 , p525 , p524 , p523 , p499 , p528 , p527 , p501 , p500 , p498 , p513 , p409 - 2 , p547 , p408 - 2 , p548 , p550 , p447 , p535 , p551 , p553 , p581 , bch - 2443 , bch - 2736 , bch - 2741 , bch - 2733 , and bch - 2444 . proteolytic stabilities of the compounds of this invention against human a - thrombin and human plasma proteases were measured as described in szewczuk et al ., 1993 , supra , and szewczuk et al ., 1992 , supra , respectively . proteolytic stability of the inhibitors against proteases on kidney membranes was measured as follows : the preparation of kidney membranes was carried out at 0 - 4 ° c . according to the procedure ( method 3 ) of maeda , t ., balakrishnan , k ., & amp ; mehdi , s . q . ( 1983 ) biochim . biophys . acta 731 , 115 - 120 . the kidneys of sprague - dawley ™ rats were minced finely with surgical scissors . the tissue ( 1 g ) was then added to 3 ml of homogenization buffer ( 10 mm sodium phosphate buffer , ph 7 . 4 , containing 1 mm mgcl2 , 30 mm nacl , 0 . 02 % nan3 and 10 μg / l of dnase ) and homogenized using a polytron * homogenizer ( brinkmann ). for sufficient cell disruption , the tissue was subject to five or six bursts for 5 seconds each time at a power setting of 7 separated by 1 to 2 minutes of cooling . about 10 ml of the homogenate was layered over 10 ml of a 41 % ( w / v ) solution of sucroseand centrifuged in a beckman sw27 ™ swinging bucket rotor ( 100000 × g for 30 minutes ). the interfacial membranes were collected and washed twice with 10 mm tris hcl buffer , ph 7 . 4 . the suspension of the membranes in the same buffer was stored in small aliquots at - 80 ° c . until they were used . the protein content of the suspension were determined before the storage by amino acid analysis . an aliquot of kidney membrane ( 3 mg ) and 3 nm of the inhibitor were then incubated in 0 . 6 ml of 10 mm sodium phosphate buffer , ph 7 . 4 , containing 1 mm mgcl2 , 30 mm nacl , 0 . 02 % nan 3 and 10 μg / l of dnase , for digestion at 37 ° c . an aliquot ( 0 . 15 ml ) of the reaction solution was sampled at 0 , 15 and 30 minutes of the reaction time . the reaction was terminated by heating at 100 ° c . in a boiling water for 2 minutes . the sample was subsequently spun at 6000 × g for 2 minutes and the supernatant was injected onto a hewlett packard model 1090 ™ hplc . the inhibitors and their metabolites were isolated on an analytical c18 column ( 4 . 6 × 250 mm , vydac *) with a linear gradient from 10 to 70 % of acetonitrile gradient containing 0 . 1 % trifluoroacetic acid over 60 minutes at a flow rate of 1 ml / min . the elution profile was monitored by the absorbance at 210 nm . the peptides were collected and identified by the amino acid analysis described in szewczuk et al ., 1992 , supra . materials . the chromogenic and fluorogenic substrates tosyl - gly - pro - arg - pna and tos - gly - pro - arg - amc were purchased from boehringer manheim and sigma , respectively . fibrinogen and bovine or human α - thrombins were from sigma and purity was confirmed by sodium inhibitor dissolved in the same buffer . initial velocities were recorded at several inhibitor concentrations and kinetic parameters were determined by fitting the data to a general equation describing enzyme inhibition ( segel , 1975 ). the data were analyzed using the non - linear regression program rnlin in the imsl library ( imsl , 1987 ) on a microvax ™ 3500 computer . dixon and lineweaver - burk plots were constructed to qualitatively assign the type of inhibition exhibited by each peptide . fluorogenic assays were conducted using the same conditions and instrument as above operating in the fluorescence mode in the ratio ( λ ex = 383 nm , λ em = 455 nm ) fluorescence intensities were calibrated with 7 - amino - 4 - methyl coumarin solution of known concentration materials . the chromogenic and fluorogenic substrates tosl - gly - pro - arg - ρna and tos - gly - pro - arg - amc were purchased from boehringer manheim and sigma , respectively . fibrinogen and bovine or human α - thrombins were from sigma and purity was confirmed by sodium inhibitor dissolved in the same buffer . the fibrin clotting assay was performed in 50 mm tris hcl buffer ( ph 7 . 52 at 37 ° c .) containing 0 . 1 m nacl and 0 . 1 % poly ( ethylene glycol ) 8000 with 9 . 0 × 10 - 10 m ( 0 . 1 nih unit / ml ) and 0 . 03 % ( w / v ) of the final concentrations of human thrombin and bovine fibrinogen , respectively , as reported elsewhere ( szewczuk et al ., 1992 ). the clotting time was plotted against the inhibitor concentrations and the ic50 was estimated as the inhibitor concentration required to double the clotting time relative to the control . the inhibition of the amidolytic activity of human thrombin was measured fluorometrically using tos - gly - pro - arg - amc as a fluorogenic substrate in 50 mm tris - hcl buffer ( ph 7 . 52 at 37 ° c .) containing 0 . 1 m nacl and 0 . 1 % poly ( ethylene glycol ) 8000 at room temperature ( szewczuk et al ., 1992 ). the final concentrations of the inhibitors , the substrate and human thrombin were 0 . 1 - 5 - fold of ki , 1 - 8 × 10 - 5 m and 6 . 0 × 10 - 11 m , respectively for the data in table 1 . for data in tables ii and iii , the corresponding concentrations were 0 . 5 -™ 1000 - fold of ki , 1 - 8 × 10 - 6 m and 3 . 0 × 10 - 11 m , respectively , if k , & gt ; 10 - 10 m , and 10 - 100 - fold of ki , 5 - 40 × 10 - 6 m and 3 . 0 10 - 11 m , respectively , if ki & lt ; 10 - 10 m . the hydrolysis of the substrate by thrombin was monitored on a varian - cary 2000 ™ spectrophotometer in the fluorescence mode ( λex = 383 nm , λem = 455 nm ) or on a hitachi f2000 ™ fluorescence spectrophotometer ( λ ex = 383 nm , λ em = 455 nm ), and the fluorescent intensity was calibrated using amc . the reaction reached a steady - state within 3 min after mixing thrombin with the substrate and an inhibitor . the steady - state velocity was then measured for a few minutes . the compounds of this invention were also pre - incubated with thrombin for 20 min at room temperature before adding the substrate . the steady - state was achieved within 3 min and measured for a few min . the kinetic data ( the steady - state velocity at various concentrations of the substrate and the inhibitors ) of the competitive inhibition was analyzed using the methods described by segel ( 1975 ). a non - linear regression program , rnlin in the imsl library ( imsl , 1987 ), lmder in minpack library ( more et al ., 1980 ) or microsoft ™ excell ™, was used to estimate the kinetic parameters ( k m v max and k i ). the biological data are reported on tables i - v . table i__________________________________________________________________________activities of the thrombin active site directed inhibitorspeptidesequence ki ( nm ) ic . sub . 50 ( nm ) __________________________________________________________________________p429 dansyl - arg -( d - pipecolic acid )- nh . sub . 2 158 ± 57 430 ± 130p428 dansyl - arg -( l - pip )- nh . sub . 2 19100 ± 1300 37900 ± 1900p431 dansyl - arg -( d - pipecolic acid )- abu - nh . sub . 2 980 ± 130 2580 ± 680p430 dansyl - arg -( l - pip )- abu - nh . sub . 2 11600 ± 3300 39100 ± 7200p396 dansyl - arg -( d - tic )- nh . sub . 2 390 ± 20 820 ± 150__________________________________________________________________________ table ii__________________________________________________________________________activity of thrombin inhibitors with various active siteinhibitor segments structure of active sitepeptide inhibitor segment k . sub . i ( nm ) __________________________________________________________________________p448 ( seq id no : 8 ) dansyl - arg -( d - pipecolic acid ). sup . a 0 . 0170 ± 0 . 0042p447 ( seq id no : 9 ) dansyl - arg -( l - pip ). sup . a 12 . 4 ± 1 . 8p471 ( seq id no : 11 ) dansyl - arg -( d - tic ). sup . a 0 . 285 ± 0 . 040p472 ( seq id no : 12 ) dansyl - arg -( d -( cha ). sup . a 17 . 1 ± 3 . 1p473 ( seq id no : 13 ) dansyl - arg - d -( acha ). sup . a 36 . 3 ± 10 . 3p476 ( seq id no : 15 ) dansyl - phe -( d - pipecolic acid ). sup . a 2 . 62 ± 0 . 20p477 ( seq id no : 16 ) dansyl - cha -( d - pipecolic acid ). sup . a 5 . 85 ± 0 . 098p493 ( seq id no : 10 ) dansyl - nle -( d - pipecolic acid ). sup . a 5 . 20 ± 1 . 31p492 ( seq id no : 14 ) dansyl -( d - arg )-( d - pipecolic acid ). sup . a 1 . 02 ± 0 . 38p531 ( seq id no : 17 ) α - nas - arg -( d - pipecolic acid ). sup . a 0 . 032 ± 0 . 001p532 ( seq id no : 18 ) β - nas - arg -( d - pipecolic acid ). sup . a 0 . 024 ± 0 . 004p556 ( seq id no : 19 ) bzs - arg -( d - pipecolic acid ). sup . a 0 . 137 ± 0 . 026p552 ( seq id no : 20 ) tbbs - arg -( d - pipecolic acid ). sup . a 0 . 0170 ± . 0004p540 ( seq id no : 22 ) tbbs - arg -( d - pipecolic acid ). sup . b 0 . 0053 ± 0 . 0006p534 ( seq id no : 21 ) (+) 10 - camphorsulfonyl - arg -( d - pipecolic acid ). sup . b 0 . 108 ± 0 . 001p481 ( seq id no : 23 ) ( d - cha )- arg -( d - pipecolic acid ). sup . a 9 . 51 ± 0 . 16p482 ( seq id no : 24 ) ( d - tic )- arg -( d - pipecolic acid ). sup . a 12 . 2 ± 3 . 2p483 ( seq id no : 25 ) ( d - phe )- arg -( d - pipecolic acid ). sup . a 54 . 9 ± 6 . 6p484 ( seq id no : 26 ) fmoc - arg -( d - pipecolic acid ). sup . a 14 . 8 ± 1 . 2 hirudin 0 . 00028__________________________________________________________________________ . sup . a the linker and exosite inhibitor segments comprise the sequence adaabu - dfeeipeeylq - oh . . sup . b the linker and exosite inhibitor segments comprise the sequence adaaca - dfeeipeeylqoh . table iii______________________________________activity of thrombin inhibitors with various linker serments atom structure of linker no . peptide segment lenght ki ( nm ) ______________________________________p514 abu - gly . sup . a 8 6800 ± 1640 ( seq id no : 27 ) p526 ava - gly . sup . a 9 4970 ± 260 ( seq id no : 28 ) p525 aca - gly . sup . a 10 3000 ± 830 ( seq id no : 29 ) p524 aha - gly . sup . a 11 1480 ± 170 ( seq id no : 30 ) p523 aca *- gly . sup . a 12 148 ± 9 ( seq id no : 31 ) p499 ada . sup . a 13 20 . 0 ± 4 . 0 ( seq id no : 32 ) p528 aca *- abu . sup . a 14 0 . 521 ± 0 . 086 ( seq id no : 33 ) p527 aua - gly . sup . a 15 0 . 0260 ± 0 . 0044 ( seq id no : 34 ) p501 gly - ada . sup . a 16 0 . 0271 ± 0 . 0067 ( seq id no : 35 ) p500 ada - gly . sup . a 16 0 . 0255 ± 0 . 0100 ( seq id no : 36 ) p498 βala - gly - gly - ava . sup . a 16 0 . 131 ± 0 . 022 ( seq id no : 37 ) p448 ada - abu . sup . a 18 0 . 0170 ± 0 . 0042 ( seq id no : 8 ) p513 ada - aca . sup . a 20 0 . 0155 ± 0 . 0026 ( seq id no : 38 ) p409 abu - gly . sup . b 8 no inhibition ( seq id no : 39 ) p547 ava - gly . sup . b 9 --( seq id no : 40 ) p408 aca - gly . sup . b 10 124 ± 61 ( seq id no : 41 ) p548 aha - gly . sup . b 11 --( seq id no : 42 ) p550 ada . sup . b 13 --( seq id no : 43 ) p447 ada - abu . sup . b 18 12 . 4 ± 1 . 8 ( seq id no : 44 ) hirudin 0 . 00028______________________________________ . sup . a the active site inhibitor and exosite inhibitor segments comprise the sequences dansylarg -( d - pipecolic acid ) and dfeeipeeylqoh , respectively . . sup . b the active site inhibitor and exosite inhibitor segments conprise the sequences densylarg -( l - pip ) and dfeeipeeylqoh , respectively . table iv__________________________________________________________________________activity of thrombin inhibitors with , various exosite inhibitor serments structure of active , site structure of , exositepeptide inhibitor segment inhibitor segment k . sub . i ( nm ) __________________________________________________________________________p535 ( seq dansyl - arg -( d - dyepipeea -( cha )-( d - . sup . 0 . 00123 ± 0 . 00026 . sup . 1id no : 45 ) pipecolic acid ). sup . a glu )- oh . sup . 0 . 0020 ± 0 . 0004 . sup . 2p551 ( seq β - nas - arg -( d - pipecolic dyepipeea -( cha )-( d - . sup . 0 . 00330 ± 0 . 00016 . sup . 1id no : 46 ) acid ). sup . a glu )- oh . sup . 0 . 0042 ± 0 . 0002 . sup . 2p553 ( seq tbbs - arg -( d - pipecolic dyepipeea -( cha )-( d - 0 . 0030 ± 0 . 0004id no : 47 ) acid ). sup . a glu )- ohp581 ( seq α - nas - arg -( d - pipecolic dyepipeea -( cha )-( d - 0 . 0145 ± 0 . 0009id no : 48 ) acid ). sup . a glu )- oh__________________________________________________________________________ . sup . a the linker segment comprise the sequences ( 12aminododecanoic acid ) ( 4aminobutyric acid ) . sup . 1 results from assay no . 1 . sup . 2 results from assay no . 2 table v__________________________________________________________________________activity of thrombin inhibitorpeptide active site linker exosite ki ic . sub . 50 ( dtt ) __________________________________________________________________________bch - 2443 tbbs - arg ( d - ada - abu dfepipy - oh 1 nm 12 . 0 nm ( seq id pipecolic acid ) no : 49 ) bch - 2736 tbbs - arg ( d - ada - abu dfepipy - oh 270 nm 1 . 1 μm ( seq id pipecolic acid ) no : 50 ) bch - 2741 tbbs - arg ( d - ada - abu dfepipy - oh not tested due to ( seq id no : pipecolic acid ) insolubility51 ) bch - 2733 brbs - arg ( d - ada - abu dfepipy - oh 0 . 8 nm 4 . 1 nm ( seq id pipecolic acid ) no : 52 ) bch - 2444 tipbs - arg ( d - ada - abu dfepipy - oh 5 . 5 nm 55 . 0 nm ( seq id pipecolic acid ) no : 53 ) __________________________________________________________________________ the fecl3 induced arterial injury model assays were conducted according to kurz , k . d ., main , r . w ., sandusky , g . e ., thrombosis research 60 ; 269 - 280 , 1990 and schumacher , w . a . et al . j . pharmacology and experimental therapeutics 267 ; 1237 - 1242 , 1993 . male , sprague - dawley ( 375 - 450 g ) are anesthetized with urethane ( 1500 mg / kg ip ). animals are laid on a heating pad which is maintained at 37 ° c . the carotid artery is approached through a midline cervical incision . carefully blunt dissection is used to expose and isolate the vessel from the carotid sheath . using forceps , the artery is lifted to provide clearance to insert two small polyethylene tubing ( pe - 205 ) underneath it . the temperature probe ( physitemp mt23 / 3 )™ is placed between the pe - 205 and the artery . the vessel temperature is monitored for 60 minutes after application of fecl 3 . vessel temperature changes are recorded on a thermister ( cole - palmer model 08533 - 41 ). injury is induced by application of a small disc ( 3 mm dia .) of whatman ™ no . 1 filter paper previously dipped in a 35 % solution of fecl 3 on the carotid artery above the temperature probe . the site of the experiment is covered with in aluminum foil in order to protect the fecl 3 from degradation by light . the time between the ferric chloride application and the time at which the vessel temperature decreases abruptly (& gt ; 2 . 4 ° c . ), is recorded as the time to occlusion ( tto ) of the vessel . before the start of the experiment , one blood sample is drawn ( 1 ml ) in a tube of 0 . 105m buffered citrate solution ( from the eye &# 39 ; s sinus ) and the animal is exsanguinated at the end . all the samples are kept on ice and centrifuged as soon as possible at 2000 rpm for 10 min ., 4 ° c . the plasma is analyzed in duplicate for activated partial thromboplastin time on a haemostasis analyzer ( stago st4 ™). from a group of four animals , two arteries are stored at - 80c for further analysis . the others are observed under a light microscope at 40 × ( leica ™) for quantification of the occlusion ( complete , partial , no occlusion ). the biological data are reported on table vi . table vi__________________________________________________________________________activity of thrombin inhibitor in a carotid injury - inducedthrombosis dose to double dose to achieve occlusion time patency at ( mg / kg i . v . 60 min . ( mg / kgpeptide active site linker exosite bolus ). sup . 1 i . v . bolus ). sup . 2__________________________________________________________________________p448 dansyl - arg -( d - ada - abu dfeeipeeylq - 1 . 0 not achieved at ( seq id no : 8 ) pipecolic acid ) oh ( n = 3 ) 2 ( n = 3 ) p531 αnas - arg ( d - ada - abu dfeeipeeylq - 0 . 5 not achieved at ( seq id no : 17 ) pipecolic acid ) oh ( n = 4 ) 2 ( n = 4 ) p540 tbbs - arg -( d - ada - aca dfeeipeeylq - 0 . 5 not achieved at ( seq id no : 22 ) pipecolic acid ) oh ( n = 4 ) 2 ( n = 4 ) p551 βnas - arg ( d - ada - abu dyepipeea - 0 . 5 - 1 1 - 2 ( seq id no : 46 ) pipecolic acid ) ( cha )-( d - glu )- oh ( n = 5 ) ( n = 5 ) p552 tbbs - arg -( d - ada - abu dfeeipeeylq - 0 . 5 ≧ 2 ( seq id no : 20 ) pipecolic acid ) oh ( n = 4 ) ( n = 4 ) p553 tbbs - arg -( d - ada - abu dyepipeea - 0 . 25 0 . 5 - 1 ( seq id no : 47 ) pipecolic acid ) ( cha )-( d - glu )- oh ( n = 4 ) ( n = 4 ) p532 βnas - arg ( d - ada - abu dfeeipeeylq - oh 0 . 5 - 1 1 - 2 ( seq id no : 18 ) pipecolic acid ) ( n = 4 ) ( n = 4 ) p581 αnas - arg ( d - ada - abu dyepipeea - 0 . 5 1 ( seq id no : 48 ) pipecolic acid ) ( cha )-( d - glu )- oh ( n = 3 ) ( n = 3 ) bch - 2443 tbbs - arg ( d - ada - abu dfepipy - oh not achieved not achieved at ( seq id no : 49 ) pipecolic acid ) at 4 4 ( n = 1 ) ( n = 1 ) bch - 2736 tbbs - arg ( d - ada - abu dfepipy - oh 4 not achieved at ( seq id no : 50 ) pipecolic acid ) ( n = 2 ) 4 ( n = 2 ) bch - 2741 tbbs - arg ( d - ada - abu dfepipy - oh not tested due to insolubility ( seq id no : 51 ) pipecolic acid ) bch - 2733 brbs - arg ( d - ada - abu dfepipy - oh not achieved not achieved at ( seq id no : 52 ) pipecolic acid ) at 2 2 ( n = 4 ) ( n = 4 ) bch - 2444 tipbs - arg ( d - ada - abu dfepipy - oh not tested due to insolubility ( seq id no : 53 ) pipecolic acid ) hirulog ™ 2 ( n = 4 ) 4 ( n = 4 ) heparin 200 u / kg not achieved at ( n = 4 ) 400 u / kg ( n = 4 ) __________________________________________________________________________ . sup . 1 control occlusion time is 19 ± 1 min ( n = 11 ) . sup . 2 as defined by no drop in vessel temperature __________________________________________________________________________ # sequence listing - ( 1 ) general information :- ( iii ) number of sequences : 57 - ( 2 ) information for seq id no : 1 :- ( i ) sequence characteristics :# acids ( a ) length : 6 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ label = g ( d ) other information :#&# 34 ; any independently acidic alpha - amino acid residue &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ label = x2d ) other information :#&# 34 ; any hydrophobic alpha - amino acid residue &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ label = g1d ) other information :#&# 34 ; any independently acidic alpha - amino acid residue &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ label = q ( d ) other information :#&# 34 ; if present , residue is derived from an l - alpha - amin - # o # a cyclic imino acid &# 34 ; r - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 5 #/ label = x3d ) other information :#&# 34 ; if present , residue is any hydrophobic # acid &# 34 ; alpha - amino - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 6 #/ label = r2d ) other information :#&# 34 ; a hydrophobic oligopeptide having all or a portion - # of seq id no : 4 &# 34 ;- ( ix ) feature : ( a ) name / key : region ( b ) location : 1 .. 6 #/ note = &# 34 ; consists of at least 6 :# imino acid residues &# 34 ; or - ( xi ) sequence description : seq id no : 1 :- xaa xaa xaa xaa xaa xaa1 5 - ( 2 ) information for seq id no : 2 :- ( i ) sequence characteristics :# acids ( a ) length : 6 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ label = v ( d ) other information :#&# 34 ; any independently hydrophobic amino acid residue &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 5 #/ label = w ( d ) other information :#&# 34 ; any independently hydrophobic amino acid residue &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 6 #/ label = x ( d ) other information :#&# 34 ; either d - glu , l - glu or gln &# 34 ;- ( xi ) sequence description : seq id no : 2 :- pro glu glu xaa xaa xaa1 5 - ( 2 ) information for seq id no : 3 :- ( i ) sequence characteristics :# acids ( a ) length : 4 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ product = &# 34 ; bala &# 34 ; er information :- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 5 - aminovaleric acid &# 34 ;- ( xi ) sequence description : seq id no : 3 :- xaa gly gly xaa - ( 2 ) information for seq id no : 4 :- ( i ) sequence characteristics :# acids ( a ) length : 6 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e # 5 ) ( b ) location : group ( 4 ,#/ label = v - w ) other information :#&# 34 ; any of the following residues : tyr - leu , tyr - ala , tyr -( beta - cy - # clohexylalanine ), ( beta - cycloh - # exylalanine )- leu ,# ala -( beta - cyclohexylalanine ), phe - tyr or ( beta - cycloh - # exylalanine )- ala &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 6 #/ label = x ( d ) other information :#&# 34 ; either d - glu or gln &# 34 ;- ( xi ) sequence description : seq id no : 4 :- pro glu glu xaa xaa xaa1 5 - ( 2 ) information for seq id no : 5 :- ( i ) sequence characteristics :# acids ( a ) length : 11 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( xi ) sequence description : seq id no : 5 :- asp phe glu glu ile pro glu glu tyr leu gl - # n # 10 - ( 2 ) information for seq id no : 6 :- ( i ) sequence characteristics :# acids ( a ) length : 11 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 10 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; l - beta - cyclohexylalanine &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 11 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - glu &# 34 ; / note =- ( xi ) sequence description : seq id no : 6 :- asp tyr glu pro ile pro glu glu ala xaa xa - # a # 10 - ( 2 ) information for seq id no : 7 :- ( i ) sequence characteristics :# acids ( a ) length : 7 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( xi ) sequence description : seq id no : 7 :- asp phe glu pro ile pro tyr1 5 - ( 2 ) information for seq id no : 8 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p448 other information :- ( xi ) sequence description : seq id no : 8 :- arg xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 9 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; l - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p447 other information :- ( xi ) sequence description : seq id no : 9 :- arg xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 10 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ product = &# 34 ; nle &# 34 ; her information :#&# 34 ; dansyl group attached &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p493 other information :- ( xi ) sequence description : seq id no : 10 :- xaa xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 11 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 1 , 2 , 3 , 4 - tetrahydroisoquinoline - 3 - carboxylic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p471 other information :- ( xi ) sequence description : seq id no : 11 :- arg xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 12 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - beta - cyclohexylalanine &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p472 other information :- ( xi ) sequence description : seq id no : 12 :- arg xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 13 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ;( d ) 1 - amino cyclohexane carboxylic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p473 other information :- ( xi ) sequence description : seq id no : 13 :- arg xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 14 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - arg ; dansyl group attached &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p492 other information :- ( xi ) sequence description : seq id no : 14 :- xaa xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 15 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p476 other information :- ( xi ) sequence description : seq id no : 15 :- phe xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 16 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; beta - cyclohexylalanine ; dansyl group attached &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p477 other information :- ( xi ) sequence description : seq id no : 16 :- xaa xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 17 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; alpha - naphthyl sulfonyl group att - # ached &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p531 other information :- ( xi ) sequence description : seq id no : 17 :- arg xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 18 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; beta - naphthyl sulfonyl : group att - # ached &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p532 other information :- ( xi ) sequence description : seq id no : 18 :- arg xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 19 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; benzyl sulfonyl groupn : attached &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p556 other information :- ( xi ) sequence description : seq id no : 19 :- arg xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 20 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; 4 - tert - butyl - benzeneon :# group attached &# 34 ; ulfonyl - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p552 other information :- ( xi ) sequence description : seq id no : 20 :- arg xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 21 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ;(+) 10 - camphorsulfonyl : group att - # ached &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; acp &# 34 ; her information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p534 other information :- ( xi ) sequence description : seq id no : 21 :- arg xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 22 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; 4 - tert - butyl - benzeneon :# group attached &# 34 ; ulfonyl - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; acp &# 34 ; her information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p540 other information :- ( xi ) sequence description : seq id no : 22 :- arg xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 23 :- ( i ) sequence characteristics :# acids ( a ) length : 16 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - beta - cyclohexylalanine &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 5 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 16 #/ label = p481 other information :- ( xi ) sequence description : seq id no : 23 :- xaa arg xaa xaa xaa asp phe glu glu ile pr - # o glu glu tyr leu gln # 15 - ( 2 ) information for seq id no : 24 :- ( i ) sequence characteristics :# acids ( a ) length : 16 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ;( d )- 1 , 2 , 3 , 4 - tetrahydroisoquinoline - 3 - carboxylic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 5 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 16 #/ label = p482 other information :- ( xi ) sequence description : seq id no : 24 :- xaa arg xaa xaa xaa asp phe glu glu ile pr - # o glu glu tyr leu gln # 15 - ( 2 ) information for seq id no : 25 :- ( i ) sequence characteristics :# acids ( a ) length : 16 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - phe &# 34 ; / note =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 5 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 16 #/ label = p483 other information :- ( xi ) sequence description : seq id no : 25 :- xaa arg xaa xaa xaa asp phe glu glu ile pr - # o glu glu tyr leu gln # 15 - ( 2 ) information for seq id no : 26 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; 9 - fluorenylmethoxycarbonyl group att - # ached &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p484 other information :- ( xi ) sequence description : seq id no : 26 :- arg xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 27 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p514 other information :- ( xi ) sequence description : seq id no : 27 :- arg xaa xaa gly asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 28 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 5 - amino valeric acid &# 34 ;- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p526 other information :- ( xi ) sequence description : seq id no : 28 :- arg xaa xaa gly asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 29 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; acp &# 34 ; her information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p525 other information :- ( xi ) sequence description : seq id no : 29 :- arg xaa xaa gly asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 30 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 7 - aminoheptanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p524 other information :- ( xi ) sequence description : seq id no : 30 :- arg xaa xaa gly asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 31 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 8 - aminocapylic acid &# 34 ;- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p523 other information :- ( xi ) sequence description : seq id no : 31 :- arg xaa xaa gly asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 32 :- ( i ) sequence characteristics :# acids ( a ) length : 14 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 14 #/ label = p499 other information :- ( xi ) sequence description : seq id no : 32 :- arg xaa xaa asp phe glu glu ile pro glu gl - # u tyr leu gln # 10 - ( 2 ) information for seq id no : 33 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 8 - aminocaproic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p528 other information :- ( xi ) sequence description : seq id no : 33 :- arg xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 34 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 11 - aminoundecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p527 other information :- ( xi ) sequence description : seq id no : 34 :- arg xaa xaa gly asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 35 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p501 other information :- ( xi ) sequence description : seq id no : 35 :- arg xaa gly xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 36 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p500 other information :- ( xi ) sequence description : seq id no : 36 :- arg xaa xaa gly asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 37 :- ( i ) sequence characteristics :# acids ( a ) length : 17 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; bala &# 34 ; er information :- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 6 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 5 - aminovaleric acid &# 34 ;- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 17 #/ label = p498 other information :- ( xi ) sequence description : seq id no : 37 :- arg xaa xaa gly gly xaa asp phe glu glu il - # e pro glu glu tyr leu # 15 - gln - ( 2 ) information for seq id no : 38 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; acp &# 34 ; her information :- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p513 other information :- ( xi ) sequence description : seq id no : 38 :- arg xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 39 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; l - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p409 other information :- ( xi ) sequence description : seq id no : 39 :- arg xaa xaa gly asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 40 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; l - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 5 - aminovaleric acid &# 34 ;- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p547 other information :- ( xi ) sequence description : seq id no : 40 :- arg xaa xaa gly asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 41 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; l - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; acp &# 34 ; her information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p408 other information :- ( xi ) sequence description : seq id no : 41 :- arg xaa xaa gly asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 42 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; l - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 7 - aminoheptanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p548 other information :- ( xi ) sequence description : seq id no : 42 :- arg xaa xaa gly asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 43 :- ( i ) sequence characteristics :# acids ( a ) length : 14 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; l - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 14 #/ label = p550 other information :- ( xi ) sequence description : seq id no : 43 :- arg xaa xaa asp phe glu glu ile pro glu gl - # u tyr leu gln # 10 - ( 2 ) information for seq id no : 44 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; l - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p447 other information :- ( xi ) sequence description : seq id no : 44 :- arg xaa xaa xaa asp phe glu glu ile pro gl - # u glu tyr leu gln # 15 - ( 2 ) information for seq id no : 45 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; dansyl group attached &# 34 ;:- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 14 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; l - beta - cyclohexylalanine &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 15 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - glu &# 34 ; / note =- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p535 other information :- ( xi ) sequence description : seq id no : 45 :- arg xaa xaa xaa asp tyr glu pro ile pro gl - # u glu ala xaa xaa # 15 - ( 2 ) information for seq id no : 46 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; beta - naphthyl sulfonyl : group att - # ached &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 14 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; l - beta - cyclohexylalanine &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 15 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - glu &# 34 ; / note =- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p551 other information :- ( xi ) sequence description : seq id no : 46 :- arg xaa xaa xaa asp tyr glu pro ile pro gl - # u glu ala xaa xaa # 15 - ( 2 ) information for seq id no : 47 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; 4 - tert - butylbenzenesulfonyl group att - # ached &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 14 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; l - beta - cyclohexylalanine &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 15 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - glu &# 34 ; / note =- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p553 other information :- ( xi ) sequence description : seq id no : 47 :- arg xaa xaa xaa asp tyr glu pro ile pro gl - # u glu ala xaa xaa # 15 - ( 2 ) information for seq id no : 48 :- ( i ) sequence characteristics :# acids ( a ) length : 15 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; alpha - naphthyl sulfonyl group att - # ached &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 14 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; l - beta - cyclohexylalanine &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 15 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - glu &# 34 ; / note =- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 15 #/ label = p581 other information :- ( xi ) sequence description : seq id no : 48 :- arg xaa xaa xaa asp tyr glu pro ile pro gl - # u glu ala xaa xaa # 15 - ( 2 ) information for seq id no : 49 :- ( i ) sequence characteristics :# acids ( a ) length : 11 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; tert - butylbenzenesulfonyl group att - # ached &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 11 #/ label = bch - 2443er information :- ( xi ) sequence description : seq id no : 49 :- arg xaa xaa xaa asp phe glu pro ile pro ty - # r # 10 - ( 2 ) information for seq id no : 50 :- ( i ) sequence characteristics :# acids ( a ) length : 11 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; tert - butylbenzenesulfonyl group att - # ached &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 11 #/ label = bch - 2736er information :- ( xi ) sequence description : seq id no : 50 :- arg xaa xaa xaa asp phe glu pro ile pro ty - # r # 10 - ( 2 ) information for seq id no : 51 :- ( i ) sequence characteristics :# acids ( a ) length : 11 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; tert - butylbenzenesulfonyl group att - # ached &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 11 #/ label = bch - 2741er information :- ( xi ) sequence description : seq id no : 51 :- arg xaa xaa xaa asp phe glu pro ile pro ty - # r # 10 - ( 2 ) information for seq id no : 52 :- ( i ) sequence characteristics :# acids ( a ) length : 11 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = &# 34 ; 4 - bromobenzenesulfonyl : group att - # ached &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 11 #/ label = bch - 2733er information :- ( xi ) sequence description : seq id no : 52 :- arg xaa xaa xaa asp phe glu pro ile pro ty - # r # 10 - ( 2 ) information for seq id no : 53 :- ( i ) sequence characteristics :# acids ( a ) length : 11 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ note = ( d ) other information : &# 34 ; 2 , 4 , 6 - tr - # iisopropylbenzensulfonyl group attached &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 2 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - pipecolic acid &# 34 ; e =- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 3 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; 12 - aminododecanoic acid &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; 4abu &# 34 ; er information :- ( ix ) feature : ( a ) name / key : peptide ( b ) location : 1 .. 11 #/ label = bch - 2444er information :- ( xi ) sequence description : seq id no : 53 :- arg xaa xaa xaa asp phe glu pro ile pro ty - # r # 10 - ( 2 ) information for seq id no : 54 :- ( i ) sequence characteristics :# acids ( a ) length : 4 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 1 #/ product = &# 34 ; bala &# 34 ; er information :- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 4 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; gamma - aminovaleric acid &# 34 ;- ( xi ) sequence description : seq id no : 54 :- xaa gly gly xaa1 - ( 2 ) information for seq id no : 55 :- ( i ) sequence characteristics :# acids ( a ) length : 11 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear # id no : 55 :( xi ) sequence description : seq - asp phe glu glu ile pro glu glu - # tyr leu gln # 10 - ( 2 ) information for seq id no : 56 :- ( i ) sequence characteristics :# acids ( a ) length : 11 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 10 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; l - beta - cyclohexylalanine &# 34 ;- ( ix ) feature : ( a ) name / key : modified - sit - # e ( b ) location : 11 #/ product = &# 34 ; other &# 34 ; r information :#&# 34 ; d - glu &# 34 ; / note =- ( xi ) sequence description : seq id no : 56 :- asp tyr glu pro ile pro glu glu ala xaa xa - # a # 10 - ( 2 ) information for seq id no : 57 :- ( i ) sequence characteristics :# acids ( a ) length : 7 amino ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear - ( xi ) sequence description : seq id no : 57 :- asp phe glu pro ile pro tyr1 5__________________________________________________________________________
hirudin is the most potent and specific thrombin inhibitor and is derived from the medicinal leech . it is reported to inhibit thrombin with an equilibrium dissociation constant value of 2 . 2 × 10 - 14 m . synthetic thrombin inhibitors have been designed based on the hirudin sequence but with a dramatically reduced size . the bulky active site inhibitor segment , hirudin 1 - 48 , has been substituted by small non - substrate type active site inhibitors of thrombin , e . g ., dansyl - arg -. the linker segment has also been modified using a combination of ω - amino acids to reduce the molecular weight but retaining sufficient length to span the two principal binding domains . among the inhibitors designed , dansyl - arg --- 4 - aminobutyric acid )- asp - tyr - glu - pro - ile - pro - glu - glu - ala --- oh showed the highest affinity and displays a competitive - type inhibition . the incorporation of the non - substrate type active site inhibitor segment and the linker of ω - amino acids into the bivalent thrombin inhibitors not only improved in vitro thrombin inhibitory activity to the pm level , overcame proteolytic susceptibility at the level of the &# 34 ; normal &# 34 ; scissile bond and confered high in vivo activity .