The composition and sequence specificity of Pro-Ala-Lys-OH for the thrombolytic activities of P6A and related oligopeptides.
The in vitro and in vivo thrombolytic activities of Ala-Arg-Pro-Ala-Lys-OH, its analogs and the related peptides were assayed. The results indicate that when (5)Lys of Ala-Arg-Pro-Ala-Lys-OH is changed into (5)Arg, and (3)Lys of Pro-Ala-Lys-OH is changed into (3)Arg the thrombolytic activities are collapsed; when Pro-Ala-Lys-OH is changed into Ala-Pro-Lys-OH, and Ala-Arg-Pro-Ala-Lys-OH is changed into Ala-Arg-Ala-Pro-Lys-OH the thrombolytic activities are also collapsed; when (5)Lys of Ala-Arg-Pro-Ala-Lys-OH is changed into (5)nLeu the thrombolytic activities are again collapsed. All of the results indicate that for the thrombolytic activities of Ala-Arg-Pro-Ala-Lys-OH and the related peptides Pro-Ala-Lys-OH exhibits either amino acid composition specificity or sequence specificity. The composition and sequence specificity of Pro-Ala-Lys-OH reflects its rule as the pharmacophore of P6A and the related peptides.
Zhao
Ming
M
College of Pharmaceutical Sciences, Peking University, Beijing 100083, PR China.
Wang
Chao
C
Liu
Jiangyuan
J
Zhou
Kexiang
K
Peng
Shiqi
S
D000818:Animals; D000991:Antithrombins / Q000737:chemistry* / Q000494:pharmacology*; D005338:Fibrin Fibrinogen Degradation Products / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar
D000991:Antithrombins; D005338:Fibrin Fibrinogen Degradation Products; D009842:Oligopeptides; C026893:fibrinogen peptide 6A