[Thrombin substrates containing aminobenzoic acids]

In order to study the interactions of synthetic substrates with the active site of thrombin the compounds of R-CO-Abz-Arg-OMe were obtained which contained, o-, m- and p-amino benzoic acids (Abz) at P2-subsite. R-CO-moiety was butyric, perfluorobutyric, benzoyl, 2-fluorobenzoyl and perfluorobenzoyl groups. Kinetic parameters of their hydrolysis by thrombin were measured and antithrombin activity was studied. Introduction of fluorine atoms into N-acyl groups caused insignificant alterations of the substrate or inhibitor properties of the compounds containing N-butyric group, but significantly influenced the substrate properties, when peptides contained N-benzoyl group. The interaction mechanism of the obtained substrates with thrombin was proposed.