Changes in fibrinogen and fibrin induced by a peptide analog of fibrinogen gamma365-380.
BACKGROUND
The effects of synthetic peptides with sequences derived from the gamma-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 gamma369-380 (NH(2)-WATWKTRWYSMK-COOH) showed the greatest impact on fibrin structure, compared with the 76 other overlapping dodecapeptides. Addition of this peptide, or peptide gamma365-380 (NH(2)-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 gamma369-380 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 gamma376 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 gamma369-380 region in the fibrinogen molecule.
I. Department of Medicine, University Hospital of Mannheim, Mannheim, Germany. carl-erik.dempfle@med.ma.uni-heidelberg.de
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Dempfle
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Bindeballe
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Münchbach
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Blume
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Borggrefe
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Mosesson
D000596:Amino Acids / Q000737:chemistry; D001792:Blood Platelets / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000737:chemistry; D005337:Fibrin / Q000096:biosynthesis*; D005340:Fibrinogen / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D006801:Humans; D046529:Microscopy, Electron, Transmission; D010455:Peptides / Q000737:chemistry; D010974:Platelet Aggregation; D011108:Polymers / Q000737:chemistry; D013916:Thrombelastography / Q000379:methods; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors
D000596:Amino Acids; D003432:Cross-Linking Reagents; D010455:Peptides; D011108:Polymers; C027539:fibrinopeptides gamma; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin