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Cardiovascular & Hematological Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5257
ISSN (Online): 1875-6182

Searching for Differences between Fibrinogen and Fibrin that Affect the Initiation of Fibrinolysis

Author(s): Russell F. Doolittle

Volume 6, Issue 3, 2008

Page: [181 - 189] Pages: 9

DOI: 10.2174/187152508784871954

Price: $65

Abstract

Although in a gross sense fibrin is merely a collection of fibrinogen molecules packed together in bundles, numerous small structural differences can arise as a result of the conversion of the soluble precursor into the gelled product. Some of the consequences are obvious, others more subtle. In one way or another, all these changes are the result of a sequence of events that includes the release of the fibrinopeptides A and B, the formation of protofibrils, the cross-linking of γ chains, the assembly into mature fibers and the cross-linking of α chains. Numerous immunologic differences between fibrinogen and fibrin have been cataloged, and putative sites for fibrin enhancing the activity of plasminogen activators have been identified. Although some conformational changes have been found by X-ray crystallography, the structural changes leading to the exposure of sites thought to bind t-PA and/or plasminogen remain to be demonstrated.

Keywords: Fibrinogen, fibrin, tissue plasminogen activator, plasminogen, conformational changes, synthetic peptide knobs


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