title: Solution structure of conformationally restricted vasopressin analogues.
abstract: In recent years, a massive effort has been directed towards designing potent and selective antagonists of neurohypophyseal hormones substituted at position 3. Modification of vasopressin at position 3 with 4,4'-biphenylalanine results in pharmacologically inactive analogues. Chemically, this substitution appears to vary only slightly from those previously made by us (1-Nal or 2-Nal), which afforded potent agonists of V(2) receptors. In this situation, it seemed worthwhile to study the structure of the analogues with 4,4'-biphenylalanine (BPhe) at position 3 in aqueous solution using NMR spectroscopy and total conformational analysis. This contribution is part of extensive studies aimed at understanding spatial structures of 3-substituted [Arg(8)]vasopressin analogues of different pharmacological properties. NMR data were used to calculate 3D structures for all the analogues using two methods, EDMC with the ECEPP/3 force field, and molecular dynamic with the simulated annealing (SA) algorithm. The structures obtained by the first method show a better fit between the NMR spectral evidence and the calculation for all the peptides.
authors.affiliation: Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland. milka@chemik.chem.univ.gda.pl
authors.forename: Emilia
authors.initials: E
authors.lastname: Trzepałka
authors.forename: Marta
authors.initials: M
authors.lastname: Oleszczuk
authors.forename: Maciej
authors.initials: M
authors.lastname: Maciejczyk
authors.forename: Bernard
authors.initials: B
authors.lastname: Lammek
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000737:chemistry; D011487:Protein Conformation; D012996:Solutions; D014667:Vasopressins / Q000737:chemistry* / Q000494:pharmacology / Q000502:physiology
chemical_list: D012996:Solutions; D014667:Vasopressins; D001127:Arginine Vasopressin; D010649:Phenylalanine