title: Characterization of the inhibition of fibrin assembly by fibrinogen fragment D.
abstract: Fragment D (Mr 100 000) prepared from a terminal plasmin digest of fibrinogen was isolated and used to study its effect on fibrin formation. Increasing amounts of fragment D added to a solution of fibrinogen and thrombin decrease the rigidity of the resultant gel (10% of control at 2 mol of fragment D/mol of fibrinogen). Half-maximal inhibition is achieved at 1 mol of fragment D/mol of fibrinogen for non-cross-linked clots and at 1/2 mol of fragment D/mol of fibrinogen for cross-linked clots. "Clottability' decreases concomitantly with the rigidity. Only small amounts of fragment D (less than 10% for non-cross-linked gels) are incorporated into the gel. Light-scattering shows an increase in the final fibre thickness at fragment D concentrations up to 2 mol of fragment D/mol of fibrinogen, from 60 molecules/cross-section for the control to 120 molecules/cross-section. Higher fragment D concentrations lead to a decrease in the final fibre thickness. The limit fibre thickness is 8 nm, with a length of 80 nm, which is equivalent to a fibrin trimer. On the basis of results of synthetic-substrate and fibrinopeptide-release assays, it is clear that thrombin inactivation is not responsible for this effect. These data suggest that fragment D may inhibit fibrin formation by blocking the bimolecular polymerization of activated fibrin monomer molecules to form protofibrils, although additional effects on subsequent assembly steps may also be involved.
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects; D003864:Depression, Chemical; D004548:Elasticity; D005337:Fibrin / Q000096:biosynthesis*; D005338:Fibrin Fibrinogen Degradation Products / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008027:Light; D011485:Protein Binding; D012542:Scattering, Radiation; D013917:Thrombin / Q000378:metabolism
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C015214:fibrinogen D fragment; D005337:Fibrin; D013917:Thrombin