The long range objective of this grant proposal is the definition of molecular structure-function relationships of certain proteins involved in blood coagulation and fibrinolysis. Attention continues to be focused on four areas, namely: 1) the localization of the Alpha-chain crosslink sites in the fibrinogen molecule; 2) further definition of the amino acid sequence of plasma and platelet fibrin stabilizing factor (FSF) and the interaction of these crosslinking enzymes with fibronogen or fibrin monomer as crosslinked fibrin is formed; 3) the biochemical characterization of human factor VIII (antihemophilic factor) and human von Willebrand factor; it is intended to identify and characterize the portions of the molecule responsible for each activity; and 4) the study of structure-function relationships of plasminogen, particularly with respect to the significance of the pre-activation peptide which is released when plasmin is formed. BIBLIOGRAPHIC REFERENCES: Ferguson, E.W., Fretto, L.J. and McKee, P.A.: A re-examination of the cleavage of fibrinogen and fibrin by plasmin. J. Biol. Chem. 250:7210 (1975). Ferguson, E.W., Fretto, L.J. and McKee, P.A.: Isolation of peptides containing the Alpha-chain crosslink acceptor sites of human fibrinogen. Clin. Res. XXIII:272A (1975).