New dipeptide fluorigenic substrates of human tissue kallikrein

V. F. Pozdnev, S. E. Rabinovich, T. S. Paskhina

Institute of Biological and Medical Chemistry, Academy of Medical Sciences of the USSR, Moscow

Abstract: Based on 4-methylcoumarinyl-7-amide (Amc) arginine and a series N-alkyloxycarbo-nyl derivatives of phenylalanine, eleven Amc-derivatives of the type ROCO-Phe-Arg-Amc (R=alkyl) were synthesized; also were n-C3H7OCO-Leu-Arg-Amc and n-C3H7OCO-D-Phe-Arg-Amc synthesized. The enzymatic hydrolysis of these compounds under the action of tissue and plasma human kallikreins were studied. Tissue kallikrein from human urine hydrolyzed the compounds with R=n-propyl and n-butyl and n-C3H7OCO-Leu-Arg-Amc more readily than the known substrates Z-Phe-Arg-Amc and H-Pro-Phe-Arg-Amc. n-C3H7OCO-D-Phe-Arg-Amc is a weak inhibitor of this enzyme (Ki=1,5 10-4 M). Human plasma kallikrein hydrolized these novel substrates at a lower rate than Z-Phe-Arg-Amc.

Russian Journal of Bioorganic Chemistry 1991, 17 (10):1352-1356

Full Text (PDF, in Russian)