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. 1978 Jul;75(7):3085–3089. doi: 10.1073/pnas.75.7.3085

Synthetic peptide derivatives that bind to fibrinogen and prevent the polymerization of fibrin monomers

Andrew P Laudano 1, Russell F Doolittle 1
PMCID: PMC392718  PMID: 277910

Abstract

A series of small peptides corresponding to the amino termini of the fibrin α- and β-chains has been synthesized. The peptides glycyl-L-prolyl-L-arginyl-L-proline and glycyl-L-prolyl-L-arginylsarcosine are potent inhibitors of fibrin polymerization. Moreover, these peptides have a natural stability stemming from their inherent resistance to proteolysis because of the involvement of amino acids in each of their peptide bonds. The peptide glycyl-L-prolyl-L-arginyl-L-proline binds to fibrinogen and to fragment D, in both cases with an association constant of approximately 5 × 104; it does not bind to fragment E. The number of binding sites is two for fibrinogen and one for fragment D. The tripeptide glycyl-L-prolyl-L-arginine binds less tightly and is less than half as effective in preventing polymerization. The peptide glycyl-L-histidyl-L-arginyl-L-proline, which corresponds exactly to the amino terminus of the fibrin β-chain, does not inhibit the aggregation of fibrin monomers under the conditions used. It does bind weakly to fibrinogen, however, suggesting the involvement of sites other than those binding the α-chain analogues. Various other peptides were found not to inhibit polymerization; these included glycine-L-proline, L-prolyl-L-arginine and glycyl-L-prolyl-L-seryl-L-proline. The last-named corresponds to the serine/arginine amino acid replacement previously reported for a defective human fibrinogen.

Keywords: intermolecular contact sites, protein-ligand interactions

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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