Influence of conformationally constrained amino acids replacing positions 2 and 3 of arginine vasopressin (AVP) and its analogues on their pharmacological properties.
Synthesis of thirteen new analogues of arginine vasopressin (AVP) has been described. Amino acid residues at positions 2 and 3 of AVP, [3-mercaptopropionic acid (Mpa)(1)]AVP (dAVP), [Mpa(1),d-Arg(8)]VP (dDAVP) and [Mpa(1),Val(4),d-Arg(8)]VP (dVDAVP) were replaced with one amino acid residue using sterically constrained non-proteinogenic amino acids, 4-aminobenzoic acid (Abz), cis-4-aminocyclohexanecarboxylic acid (ach) or its trans-isomer (Ach). In the case of a potent V(1a) antagonist, [1-mercaptocyclohexaneacetic acid (Cpa)(1)]AVP, only one similar analogue has been prepared by replacing positions 2 and 3 with Abz. Unfortunately, all new peptides were inactive in bioassays for the pressor, antidiuretic and uterotonic in vitro activities in the rat.
Sobolewski
Dariusz
D
Faculty of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland. dareks@chem.univ.gda.pl
Prahl
Adam
A
Derdowska
Izabela
I
Kwiatkowska
Anna
A
Slaninová
Jirina
J
Lammek
Bernard
B
D015097:3-Mercaptopropionic Acid / Q000737:chemistry; D010129:4-Aminobenzoic Acid / Q000737:chemistry; D000595:Amino Acid Sequence; D000598:Amino Acids, Cyclic / Q000737:chemistry*; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry; D004232:Diuretics / Q000494:pharmacology; D005260:Female; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D001743:Urinary Bladder / Q000187:drug effects; D014599:Uterus / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000598:Amino Acids, Cyclic; D003509:Cyclohexanecarboxylic Acids; D004232:Diuretics; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; C010124:4-aminocyclohexanecarboxylic acid; D015097:3-Mercaptopropionic Acid; D010129:4-Aminobenzoic Acid