Changes in fibrinogen and fibrin induced by a peptide analog of fibrinogen γ365-380

Abstract

Background: The effects of synthetic peptides with sequences derived from the γ-chain of fibrinogen on the functional properties of fibrinogen and fibrin were investigated. Methods: Methods included thrombelastography, clot turbidity measurement, clot elasticity measurement, platelet aggregation, and scanning transmission electron microscopy (STEM). Results: Peptide γ 369-380 (NH2-WATWKTRWYSMK-COOH) showed the greatest impact on fibrin structure, compared with the 76 other overlapping dodecapeptides. Addition of this peptide, or peptide γ365-380 (NH2-NGIIWATKTREWYSMK-COOH) to a mixture of fibrinogen and thrombin resulted a shorter clotting time, higher clot turbidity, lower clot elastic modulus, a higher degree of D-trimer and D-tetramer formation, and impaired plasmin proteolysis of the clot. In STEM, fibrin formed in the presence of peptide γ369-380 consisted of a more extensive array of linear fibrils typically consisting of 20 or more molecules. Fibrils were better organized than those from non-peptide containing mixtures. Conclusions: Replacement of the tryptophan residue γ376 massively reduced the effect of the peptide on fibrin structure. Binding of the peptide to fibrinogen induces conformational changes, which result in accelerated clotting and increased lateral association of fibrin protofibrils. The results imply a relevant functional role of sites interacting with peptide γ369-380 region in the fibrinogen molecule. © 2007 International Society on Thrombosis and Haemostasis.