Lugovska N. The discovery of a neoantigenic determinant in fibrin molecule and the finding of its functional role

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0410U005179

Applicant for

Specialization

  • 03.00.04 - Біохімія

05-07-2010

Specialized Academic Board

Д 26.240.01

Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine

Essay

Object: fibrin, fibrin-specific monoclonal antibodies, soluble fibrin. Aim: to localize neoantigenic determinants in the fibrin molecule using fibrin-specific mAbs, to determine their possible functional role in fibrin polymeryzation process and carry out immunoenzyme method of soluble fibrin quantification in human blood plasma. Methods: preparative, spectrophotometrical, immunochemical, electron micrscopy, statistical approach. Results: by using fibrin-specific mAbs obtained unknown neoantigenic determinant in coiled-coil fragment B 118-134 of fibrin molecule has been revealed; the existence of unknown site of polymerization in the fibrin fragment B 121-1138, which functions at the stage of protofibril lateral association has been shown. The double sandwich ELISA method for quantitative measurement of soluble fibrin in human blood plasma has been designed and tested in clinics. Novelty: For the first time we showed the existence of previously unknown neoantigenic determinant in the fragment B 118-134, which exposes upon transformation of fibrinogen into fibrin desAA and disappears after plasmin hydrolysis of fibrin. For the first time the existence of unknown site of polymerization in the fibrin fragment B 121-1138, which functions at the stage of protofibril lateral association has been shown. It was shown that fibrin-specific mAbs with epitopes in the region of B 118-134 are characterized by high specificity and affinity to fibrin and are of great value for soluble fibrin measurement in blood plasma. Field of the use: biochemistry, immunochemistry, immunology, medicine.

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