title: Biologically active analogues of arginine vasopressin containing conformationally restricted dipeptide fragments.
abstract: 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.
authors.affiliation: Faculty of Chemistry, University of Gdañsk, Poland. bernard@hebe.chem.univ.gda.pl
authors.forename: B
authors.initials: B
authors.lastname: Lammek
authors.forename: M
authors.initials: M
authors.lastname: Czaja
authors.forename: I
authors.initials: I
authors.lastname: Derdowska
authors.forename: E
authors.initials: E
authors.lastname: Lempicka
authors.forename: P
authors.initials: P
authors.lastname: Sikora
authors.forename: W
authors.initials: W
authors.lastname: Szkróbka
authors.forename: H I
authors.initials: HI
authors.lastname: Trzeciak
mesh_terms: 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
chemical_list: D004151:Dipeptides; D014662:Vasoconstrictor Agents; C111634:argipressin, Cpa(1)-Phe(ethylene)Phe(2,3)-Val(4)-; D001127:Arginine Vasopressin; D010649:Phenylalanine