The influence of 1-aminocyclopentane-1-carboxylic acid at position 2 or 3 of AVP and its analogues on their pharmacological properties.
This study describes the synthesis and some pharmacological properties of eight new analogues of arginine vasopressin (AVP) substituted at position 2 or 3 with cycloleucine (1-aminocyclopentane-1-carboxylic acid, Apc). All new peptides were tested for their pressor, antidiuretic and uterotonic in vitro potency. The Apc3 modification resulted in an almost complete loss of potency in all three tests, which is interpreted as a loss of interaction with all three neurohypophyseal hormone receptors. On the other hand, the Apc2 modification resulted in compounds having differently modified activities (high antidiuretic potency, low and graded pressor activity and either no activity or low oxytocin antagonizing activity in the uterotonic in vitro test) thus selectively altering the interaction with the receptors similar to that of 1-aminocyclohexane-1-carboxylic acid (Acc). The results obtained may be helpful for designing new analogues of arginine vasopressin.
Kowalczyk
Wioleta
W
Department of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland. wiola@chem.univ.gda.pl
Prahl
Adam
A
Dawidowska
Olga
O
Derdowska
Izabela
I
Sobolewski
Dariusz
D
Hartrodt
Bianca
B
Neubert
Klaus
K
Slaninová
Jirina
J
Lammek
Bernard
B
D000598:Amino Acids, Cyclic / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000737:chemistry*; D004231:Diuresis / Q000187:drug effects; D005260:Female; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000187:drug effects
D000598:Amino Acids, Cyclic; D001127:Arginine Vasopressin; C023863:1-aminocyclopropane-1-carboxylic acid