Synthesis of Modified Fragments of Fibrinogen and Their Effect on the Activity of Proteolytic Enzymes

V. N. Nikandrov ^b , N. S. Pyzhova ^b , V. P. Golubovich ^a , O. V. Mel’nik ^a , and V. P. Martinovich ^{a #}

^# Phone: +375 (17) 2648263; e-mail: vermar@iboch.bas-net.by

^a Institute of Bioorganic Chemistry , National Academy of Sciences of Belarus , ul. akademika Kuprevicha 5/2, Minsk, 220141 Belarus

^b Institute of Physiology , National Academy of Sciences of Belarus , ul. Akademicheskaya 28, Minsk , 220141 Belarus

Received August 30, 2005; in final form, October 27, 2005

Abstract: New analogues of the Gly-Pro-Arg and Arg-Gly-Asp fragments of fibrinogen were synthesized: Gly-Pro-Arg-Pro (I), Gly-Pro-Arg-Pro-Met-OMe (II), Gly-Pro-Arg-Pro-Phe (III), Gly-Pro-Arg-Pro-Asp (IV), Gly-Pro-Arg-Pro-Glu (V), and Arg-Asn-Trp-Asp (VI). Their effect on the activity of proteases of various types was studied with the method of lysis of fibrin plates. All the peptides were found to inhibit plasmin activity (by 60–85%) and the γ-subunit of nerve growth factor (by 55–93%). Tetrapeptide (VI) proved to be an effective inhibitor of tissue activator of plasminogen and the γ-subunit of nerve growth factor (by 96 and 93%, respectively). The peptides exerted practically no effect on the activity of urokinase and moderately inhibited the activity of streptokinase [(III), (IV), and (VI)], papain [(I), (II), (IV), and (VI)], subtilisin [(V) and (VI)], α-chymotrypsin [(III), (V), and (VI)], and Bacillus subtilis metalloprotease (VI). They inhibit trypsin [except for (I) and (III)] when applied on fibrin plates at a concentration of 1 × 10^–2 M, while, at a concentration of 1 × 10^–3 M, (I) and (II) induced an increase in proteolytic activity by 35 and 47%, respectively.

Key words: fragments of fibrinogen, synthesis of analogues, effect on activity of proteases

Russian Journal of Bioorganic Chemistry 2006, 32 (2):129-135