Relationship between site of sulfate groups in cellulose sulfate and their anticoagulation activity
Three cellulose sulfates (CS) with their sulfate groups only at C_-6 position (CS_C6), only at C_-2 position (CS_C2), and at some C_-6 C_-2 positions (CS_C6,2) were prepared respectively by the direct sulfation method and the regioselective sulfation method. To reveal the structure-activity relationship between sulfate groups and anticoagulation activities of CS, their anticoagulation activities were investigated by measurement of coagulation time and coagulation factor activity assays. It was indicated that CS_C6,2 could significantly prolong thrombin time (t_TT) and inhibit the activity of coagulation factor Ⅱa, also CS_C2 had a pronounced activity of prolongation of activated partial thromboplastin time (t_APTT) and inhibition of the coagulation factor Ⅹa. Comparatively the anticoagulation activity and the inhibition of the coagulation factors of CS_C6 were weaker than those of CS_C6,2 or CS_C2. The site of the sulfate groups in CS influnced the flexibility and conformation of the glycan chains, resulting in the different affinity of CS and antithrombin Ⅲ (AT Ⅲ).Thus, the prolongation of t_APTT t_TT and the inhibition of Ⅱa Ⅹa of CS was associated with the site of the sulfate groups in CS.