Analogues of arginine vasopressin modified in position 2 or 3 with naphthylalanine: selective antagonists of oxytocin in-vitro.
In this study we describe the synthesis and some pharmacological properties of six new analogues of arginine vasopressin (AVP). Five of the peptides were substituted in position 2 with L-1-naphthylalanine (L-1-Nal) or D-1-naphthylalanine (D-1-Nal); one had D-1-Nal in position 3. All analogues were tested in bioassays for pressor and antidiuretic activity. We also tested the uterotonic activity of the peptides in-vitro. Two of the new peptides were moderately potent V1a and oxytocin antagonists. The modifications proposed resulted in a drop or the removal of antidiuretic activity and in the removal of pressor activity, or conversion into moderate antagonists. Two peptides ([Mpa1, (L-1-Nal)2]AVP and [Mpal, (D-1-Nal)2]AVP) which appear not to interact with V1a and V2 receptors were exceptionally selective oxytocin antagonists in vitro. These compounds with selective oxytocin antagonistic activity may be promising candidates for the development of potential tocolytic agents for the prevention of pre-term labour.
Sobocińska
M
M
Faculty of Chemistry, University of Gdañsk, Poland.
Lempicka
E
E
Konieczna
E
E
Derdowska
I
I
Lammek
B
B
Melhem
S
S
Kozik
W
W
Janecka
J
J
Janecki
M
M
Trzeciak
H I
HI
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D010121:Oxytocin / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014599:Uterus / Q000187:drug effects
D001127:Arginine Vasopressin; D010121:Oxytocin