Synthesis and biological activity of nitronyl nitroxide containing peptides.
[1-(1',3'-Dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetic acid (4), a nitronyl nitroxide, and its peptide derivatives, N-[1-(1',3'-dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetyl-ARPAK (9a), -GRPAK (9b), and -QRPAK (9c), were synthesized and characterized. Judging from the results of electron spin resonance analysis, the newly synthesized nitronyl nitroxide containing peptides, 9a, 9b, and 9c, demonstrated the characteristics of free radicals. The free radical scavenging activities of 9a, 9b, and 9c were assessed using in vitro free radical scavenging tests. The thrombolysis effect of 9a, 9b, and 9cwas evaluated using an euglobulin clot lysis test, a fibrinolytic lysis test, and in vivo thrombolysis tests. Results indicated that these nitronyl nitroxide containing peptides possessed both free radical scavenging activity and thrombolytic activity.
College of Pharmaceutical Sciences, Peking University, Beijing 100083, PR China.
Ming
M
Zhao
Junling
J
Liu
Chao
C
Wang
Lili
L
Wang
Hu
H
Liu
Shiqi
S
Peng
D000595:Amino Acid Sequence; D000818:Animals; D003497:Cyclic N-Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016716:PC12 Cells; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010673:Pheochromocytoma; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship
D003497:Cyclic N-Oxides; D005343:Fibrinolytic Agents; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides; D010455:Peptides