Pozniak T. Localization of the new fibrin polymerization sites and search of low-molecular compounds which block this process

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0412U003250

Applicant for

Specialization

  • 03.00.04 - Біохімія

14-05-2012

Specialized Academic Board

Д 26.260.01

Essay

The object: fibrinogen, fibrins desA and desAВ of human, fibrin polymerization. The aim: to localize the unknown sites of fibrin polymerization to establish the spatial orientation and the functional role of the аlphaС-regions of fibrinogen molecule in the process of it consecutive transformations in fibrins desA and desAB, to find the low-molecular compounds which specifically inhibit of fibrin polymerization which prevent thrombosis. Methods: hybridoma technology, methods of preparative and analitical biochemistry, ELISA, Western blot analysis, SPR-analysis, turbidity analysis, electron microscopy, determination of PT and APTT, statistical analysis It was established that the аlfaС-regions in the molecules of fibrinogen, monomer and polymer of fibrin desA associated with FpB and after cleavage FpB the аlphaС-regions distance from the core of the formed fibrin desAB accelerating the process of protofibryl orientation by interacting between the molecules. It was localized previously unknown fibrin polymerization sites - Аalpha195-205 and gamma69-77. It was found for the first time the highly effective low-molecular weight compounds which inhibitor of fibrin polymerization and clotting of human blood plasma - 5,11,17,23-tetrakis [bis(dihydroxy phosphoryl)methyl]-calix[4]arene (C-192) and its sodium salt (C-145), which can be used as the basis for the design of antithrombotic drugs. Scope -medical-biological.

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