Effect of calcium and synthetic peptides on fibrin polymerization.
Human fibrinogen was subjected to limited proteolytic attack by thrombin, batroxobin or Agkistrodon contortrix thrombin-like enzyme, yielding desAB-, desA- or desB-fibrin monomers, respectively. Turbidity curves demonstrated that, with all three enzymes, the polymerization process was strongly accelerated by increasing the calcium concentration from 10(-5) M to 10(-4) M. Synthetic peptide Gly-His-Arg (5 mM), an analogue of the aminoterminal sequence of fibrin beta-chain, inhibited aggregation of desB-fibrin monomers at physiological calcium concentration whereas it enhanced aggregation of desA- and desAB-fibrin monomers at calcium concentrations below 10(-4) M. On the other hand, Gly-Pro-Arg (1 mM) corresponding to the amino-terminus of fibrin alpha-chain, dramatically inhibited aggregation of both desA- and desB-fibrins, but it only moderately affected the polymerization of thrombin-induced monomers. We conclude that the observed effects of Gly-Pro-Arg and Gly-His-Arg are not due solely to their competition with fibrin amino-termini for the respective binding sites in the D-domain, but rather reflect conformational changes in fibrin monomers which affect the polymerization process.
D012103:Batroxobin / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology*; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism
D009842:Oligopeptides; C035024:glycyl-prolyl-arginine; C035023:glycyl-histidyl-arginine; D005337:Fibrin; D012103:Batroxobin; D013917:Thrombin; D002118:Calcium