Biologically active analogues of arginine vasopressin containing conformationally restricted dipeptide fragments.
In this study we described the synthesis and pharmacological properties of five new analogues of arginine vasopressin (AVP). Four of these analogues contained ethylene-bridged dipeptide Phe-Phe in positions 2 and 3; one had two N-Me-Phe residues. All new peptides were tested for vasopressor and antidiuretic activities. We also estimated the uterotonic activities of these compounds in vitro. Three analogues were highly potent V1-antagonists. One of them, namely [Cpa1,(Phe-Phe)2,3,Val4]AVP, which seemed to not interact with either V2 and oxytocic receptors, was outstandingly selective. It is interesting that the high antipressor potency of our second peptide, [(N-Me-Phe)2,3]AVP, was achieved without modification of position 1. Our results open new possibilities for the design of very potent and selective V1-antagonists of AVP.
Lammek
B
B
Faculty of Chemistry, University of Gdañsk, Poland. bernard@hebe.chem.univ.gda.pl
Czaja
M
M
Derdowska
I
I
Lempicka
E
E
Sikora
P
P
Szkróbka
W
W
Trzeciak
H I
HI
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004151:Dipeptides / Q000737:chemistry*; D004231:Diuresis / Q000187:drug effects; D005260:Female; D008297:Male; D010649:Phenylalanine / Q000737:chemistry; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014599:Uterus / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004151:Dipeptides; D014662:Vasoconstrictor Agents; C111634:argipressin, Cpa(1)-Phe(ethylene)Phe(2,3)-Val(4)-; D001127:Arginine Vasopressin; D010649:Phenylalanine