Analogues of arginine vasopressin modified in the N-terminal part of the molecule with enantiomers of N-methylphenylalanine.
Four new analogues of arginine vasopressin (AVP) substituted in positions 2 and 3 with all possible combinations of enantiomers of N-methylphenylalanine were synthesized and studied to assess the influence of N-methylation of the peptide bonds between the first three amino acids on the pharmacological properties of the resulting peptides. The next three analogues were designed to learn how the shortening of the peptide chain, by removal of one of the N-methylphenylalanine residues, would affect pharmacological properties of the resulting compounds. The activity of the analogues was tested in the in vitro uterotonic, pressor and antidiuretic tests. None of the prepared analogues displayed significant biological activity with the exception of [Me-d-Phe(2), Me-Phe(3)]AVP and [Me-d-Phe(2,3)]AVP, which showed low antiuterotonic activity (pA(2) = 6.6 and pA(2) = 6.4, respectively). Our results, while not impressive in terms of biological activity, may be helpful for designing potent and selective oxytocin antagonists.
Kowalczyk
W
W
Department of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland. wiola@chemik.chem.univ.gda.pl
Derdowska
I
I
Dawidowska
O
O
Prahl
A
A
Hartrodt
B
B
Neubert
K
K
Slaninová
J
J
Lammek
B
B
D000818:Animals; D001127:Arginine Vasopressin / Q000032:analysis / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004151:Dipeptides / Q000737:chemistry; D004231:Diuresis / Q000187:drug effects*; D005260:Female; D008745:Methylation; D051381:Rats; D017208:Rats, Wistar; D014590:Uterine Contraction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004151:Dipeptides; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin