title: Non-sequential vasopressin peptides. Stereochemistry and biological activity.
abstract: Two cyclic disulfides of structure Cys-Tyr-Arg-Arg-Tyr-Cys-NH2 (1) and Cys-Tyr(Me)-Arg-Arg-Tyr(Me)-Cys-NH2 (2), two nonapeptide derivatives of 1 extended at the C-terminal with Pro-Arg-Gly-NH2 (3) or Pro-D-Arg-Gly-NH2 (4) and derivatives of 3 and 4 having Mpr in position 1, i.e. analogs (5) and (6), respectively, were synthesized, and their stereochemistry and biological activity were studied. All the peptides displayed low dose-dependent uterotonic activity in vitro and antidiuretic activity in vivo. None of the peptides increased the blood pressure of the experimental animals. Compounds 2, 4 and 6 showed a low inhibitory effect on AVP pressor activity; compound 6, in addition, displays a significant and long-lasting vasodepressor effect. NMR measurements indicated the existence of hydrogen bond between the amino acid residues in positions 2,5 and 3,4 of peptides 1 and 2, and side-chain interactions between amino acid residues in positions 2,3 and 4,5 of peptide 1. No such side-chain interactions were detected in peptide 2.
authors.affiliation: Na Loukoti, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Zaoral
authors.forename: I
authors.initials: I
authors.lastname: Bláha
authors.forename: M
authors.initials: M
authors.lastname: Budesínský
authors.forename: A
authors.initials: A
authors.lastname: Machová
authors.forename: J
authors.initials: J
authors.lastname: Slaninová
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D003894:Deamino Arginine Vasopressin / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D008274:Magnesium / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010452:Peptide Biosynthesis; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D051381:Rats; D013237:Stereoisomerism; D014443:Tyrosine / Q000737:chemistry; D014667:Vasopressins / Q000737:chemistry*
chemical_list: D010455:Peptides; D014667:Vasopressins; D014443:Tyrosine; D001120:Arginine; D003894:Deamino Arginine Vasopressin; D008274:Magnesium; D003545:Cysteine