Analogs of arginine vasopressin modified in the N-terminal part of the molecule with a conformationally constrained cis-peptide bond motif.
The present work is part of our studies aimed at clarifying the influence of steric constraints in the N-terminal part of arginine vasopressin (AVP) and its analogs on the pharmacological activity of the resulting peptides. We describe the synthesis of eight new analogs of AVP or [3-mercaptopropionic acid (Mpa)]AVP (dAVP) substituted at positions 2 and 3 or 3 and 4 with two diastereomers of 4-aminopyroglutamic acid. The steric constraints provided by this modification turned out, however, so strong that all the peptides were inactive in all of the bioassays (pressor, antidiuretic and uterotonic tests).
Sobolewski
Dariusz
D
Faculty of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland. dareks@chem.univ.gda.pl
Prahl
Adam
A
Derdowska
Izabela
I
Slaninová
Jirina
J
Kaczmarek
Krzysztof
K
Zabrocki
Janusz
J
Lammek
Bernard
B
D000595:Amino Acid Sequence; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004967:Estrogens / Q000502:physiology; D005260:Female; D008297:Male; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000187:drug effects / Q000502:physiology; D014667:Vasopressins / Q000494:pharmacology
D004967:Estrogens; D009842:Oligopeptides; D014667:Vasopressins; D001127:Arginine Vasopressin