[Analysis of the relationship between the reactivity of synthetic substrates and thrombin inhibitors and their structure].
Kinetics of thrombin- and trypsin-catalyzed hydrolysis of diphenylacetyl-L-arginine esters was studied at pH 8.5 and 25 degrees C, and the antithrombin activity of in vitro synthesized compounds was examined. The anticlotting activity of arylsulphonyl-L-arginine methyl esters appeared to be higher than that of the derivatives of diphenyl arginine. Relations were found connecting polar (delta) and steric (Es) characteristics of substituent (R) in R-C6H4-SO2-Arg-OCH3 esters with their antithrombin activity in vitro or with efficiency of their thrombin-catalyzed hydrolysis. This gives supplementary possibilities for synthesis of new substrates and more potent thrombin inhibitors.
D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004158:Diphenylacetic Acids / Q000494:pharmacology*; D006868:Hydrolysis; D007700:Kinetics; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013917:Thrombin / Q000032:analysis / Q000037:antagonists & inhibitors*; D014106:Tosylarginine Methyl Ester / Q000031:analogs & derivatives / Q000494:pharmacology*; D014357:Trypsin / Q000032:analysis
D004158:Diphenylacetic Acids; D014106:Tosylarginine Methyl Ester; D001120:Arginine; D014357:Trypsin; D013917:Thrombin
Issledovanie zavisimosti reaktsionnoĭ sposobnosti sinteticheskikh substratov i ingibitorov trombina ot ikh stroeniia.