Synthesis and thrombolytic activity of pseudopeptides related to fibrinogen fragment.
Two kinds of linkers consisting of 3-(S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, ARPAK, GRPAK and QRPAK were synthesized. The thrombolytic activities in vivo indicated that the coupling position of 3-(S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid in the peptides effected on the potencies significantly. When the C-terminal of the peptides was amidated by 3-(S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, the thrombolytic potency of the peptides was enhanced or kept. When the N-terminal of the peptides was acylated by 3-(S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, however, the thrombolytic effect of the peptides was banished. The expected specific beta II'-turn conformation and the stability to trypsin in the pseudopeptides with 3-(S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid in its C-terminal may be responsible for the enhanced thrombolytic potency.
Wu
Yanfen
Y
College of Pharmaceutical Chemistry, Peking University, Beijing, PR China.
Zhao
Ming
M
Wang
Chao
C
Peng
Shiqi
S
D000818:Animals; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004355:Drug Stability; D005338:Fibrin Fibrinogen Degradation Products / Q000737:chemistry*; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010434:Pepsin A / Q000494:pharmacology; D017433:Protein Structure, Secondary; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013927:Thrombosis / Q000188:drug therapy
D003432:Cross-Linking Reagents; D005338:Fibrin Fibrinogen Degradation Products; D005343:Fibrinolytic Agents; D009842:Oligopeptides; D010434:Pepsin A