title: Analogues of arginine vasopressin modified in position 2 and 3 with conformationally constrained dipeptide fragments.
abstract: This study describes the synthesis and some pharmacological properties of ten new analogues of arginine vasopressin (AVP) containing a conformationally constrained dipeptide fragment in the N-terminal part of their molecules. Amino acid residues in positions 2 and 3 of AVP and some of its agonistic analogues were replaced with -Phe-Phe and D-Phe-D-Phe, dipeptides having a -CH2-CH2- link bridging two nitrogens. All the new peptides were tested for vasopressor and antidiuretic activities. Four peptides with pA2 values ranging from 5.96 to 7.21 turned out to be weak or moderately potent V1a antagonists. The results supplied new information about the structure-activity relationship of AVP analogues. As some of these were unexpected, they point to the need for caution when extrapolating previously known effects of modifications to analogues having conformationally constrained fragments in their molecules.
authors.affiliation: Department of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Łempicka
authors.forename: Izabela
authors.initials: I
authors.lastname: Derdowska
authors.forename: Wioleta
authors.initials: W
authors.lastname: Kowalczyk
authors.forename: Olga
authors.initials: O
authors.lastname: Dawidowska
authors.forename: Adam
authors.initials: A
authors.lastname: Prahl
authors.forename: Marcin
authors.initials: M
authors.lastname: Janecki
authors.forename: Tomasz
authors.initials: T
authors.lastname: Jasiński
authors.forename: Henryk I
authors.initials: HI
authors.lastname: Trzeciak
authors.forename: Bernard
authors.initials: B
authors.lastname: Lammek
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology; D004232:Diuretics / Q000037:antagonists & inhibitors; D004573:Electrolytes / Q000652:urine; D008297:Male; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D004151:Dipeptides; D004232:Diuretics; D004573:Electrolytes; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin