Influence of enantiomers of 1-naphthylalanine in position 2 of VAVP and dVAVP on their pharmacological properties.
In this study, we described the synthesis and some pharmacological properties of four new analogues of arginine vasopressin (AVP). Two peptides are substituted in position 2 with L-1-naphthylalanine (L-1-Nal) or its D-enantiomer and in position 4 with valine. In the further two compounds, we combined the above modifications with placement into position 1 of 3-mercaptopropionic acid residue (Mpa). All new peptides were tested for vasopressor and antidiuretic activities. We also estimated the uterotonic activities of these compounds in vitro. Urine samples prior and after peptide administration were analyzed for electrolytes excretion. All analogues are potent oxytocin antagonists. One of them, namely [L-1-Nal2,Val4]AVP, which appears practically not to interact with V1a and V2 receptors, is exceptionally selective. Our results open new possibilities for the design of very potent and selective oxytocin antagonists in vitro.
Derdowska
Izabela
I
Department of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland.
Prahl
Adam
A
Kowalczyk
Wioleta
W
Janecki
Marcin
M
Melhem
Samed
S
Trzeciak
Henryk I
HI
Lammek
Bernard
B
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004573:Electrolytes / Q000652:urine; D007536:Isomerism; D008297:Male; D010121:Oxytocin / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000494:pharmacology
D004573:Electrolytes; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; D010121:Oxytocin