Effect of Calcium and Synthetic Peptides on Fibrin Polymerization

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Abstract
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 β-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 α-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.