Platelet aggregation inhibitors

Details Platelet aggregation inhibitors Platelet aggregation inhibitors

C - Chemistry, Metallurgy

07

K

C07K 7/64 (2006.01) A61K 38/08 (2006.01) A61K 38/12 (2006.01) A61P 7/02 (2006.01) C07K 7/06 (2006.01) C07K 14/75 (2006.01)

Patent

CA 2388770

An assay for screening snake venom for the presence or absence of platelet aggregation inhibitors (PAIs) based on specific receptor binding is described. Using this assay, the identification and characterization of PAIs in a wide range of snake venom samples was accomplished. The isolated and purified PAI from several of these active snake venoms is described and characterized. In addition, PAIs lacking the Arg-Gly-Asp (RGD) adhesion sequence but containing K* -(G/Sar)-D wherein K* is a modified lysyl residue of the formula R12 N(CH2)4CHNHCO- wherein each R1 is independently H, alkyl(1-6C) or at most one R1 is R2-C=NR3 wherein R2 is H, alkyl(1-6C), phenyl or benzyl, or is NR4 in which each R4 is independently H or alkyl(1-6C) and R3 is H, alkyl(1-6C), phenyl or benzyl, or R2-C=NR3 is a radical selected from the group consisting of (a), (b), (c) and (d) where m is an integer of 2-3, and each R5 is independently H or alkyl(1-6C); and wherein one or two (CH2) may be replaced by O or S provided said O or S is not adjacent to another heteroatom are prepared and shown to specifically inhibit the binding of fibrinogen or von Willebrand Factor to GP IIb- IIIa.

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