Method utilizing purified GP IIb-IIIa to detect the presence of platelet aggregation inhibitors

US5736339A · kind A · utility

Assignee

• COR Therapeutics, Inc. · US

Inventors

• Robert M. Scarborough · Belmont, US
• David L. Wolf · Palo Alto, US
• Israel Charo · Lafayette, US

Key dates

• Filing date: Jun 5, 1995
• Grant date: Apr 7, 1998
• Expiry date: Jun 5, 2015

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K14/78
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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 PA1 R.sup.1.sub.2 N(CH.sub.2).sub.4 CHNHCO-- wherein each R.sup.1 is independently H, alkyl(1-6C) or at most one R.sup.1 is R.sup.2 --C.dbd.NR.sup.3 wherein R.sup.2 is H, alkyl(1-6C) or is NR.sup.4.sub.2 in which each R.sup.4 is independently H or alkyl(1-6C) and R.sup.3 is H, alkyl(1-6C), phenyl or benzyl, or R.sub.2 --C.dbd.NR.sup.3 is a radical selected from the group consisting of: ##STR1## where m is an integer of 2-3, and each R.sup.5 is independently H or alkyl(1-6C); PA1 and wherein one or two (CH.sub.2) may be replaced by O or S provided said O or S is not adjacent to another heteroatom PA1 are prepared and shown to specifically inhibit the binding of fi…