Synthesis and thrombolytic activity of fibrinogen fragment related cyclopeptides.
In the modification of the fibrinogen fragment related sequences ARPAK, QRPAK GRPAK and KRPAK, the corresponding cyclo-ARPAK, cyclo-QRPAK, cyclo-GRPAK, and cyclo-KRPAK were prepared in the diluted solution. The bioassay in vivo indicated that the thrombolytic potencies of cyclo-ARPAK, cyclo-GRPAK, cyclo-QRPAK, and cyclo-KRPAK were significantly higher than that of ARPAK, QRPAK, GRPAK, and KRPAK. In water, the cyclopeptides were incubated with pepsin or trypsin at 37 degrees C for 64 h. There was no degradation product observed, on the other hand, with the same condition, the peptides were completely hydrolyzed in 8 h. The relationships among the rigidity or the conformation and the thrombolytic activity in vivo and the stability to enzyme-induced hydrolysis in vitro of the cyclopeptides were discussed.
Zhao
Ming
M
College of Pharmaceutical Sciences, Peking University, Beijing 100083, PR, China.
Lin
Na
N
Wang
Chao
C
Peng
Shiqi
S
D000595:Amino Acid Sequence; D000818:Animals; D004355:Drug Stability; D005338:Fibrin Fibrinogen Degradation Products / Q000737:chemistry*; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D006868:Hydrolysis; D008297:Male; D010434:Pepsin A / Q000378:metabolism / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D017433:Protein Structure, Secondary; D051381:Rats; D017208:Rats, Wistar; D014357:Trypsin / Q000378:metabolism / Q000494:pharmacology
D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; D010456:Peptides, Cyclic; D014357:Trypsin; D010434:Pepsin A