Conformational solution studies of [Sar7]desamino- and [MeAla7]desamino- vasopressin analogues using NMR spectroscopy

✍ Scribed by Sylwia Rodziewicz-Motowidło; Igor Zhukov; Franciszek Kasprzykowski; Zbigniew Grzonka; Jerzy Ciarkowski; Dr Jacek Wójcik

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 259 KB
• Volume: 8
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.394

✦ Synopsis

Abstract

Solution structures of two analogues of vasopressin with an amino acid sequence of c[Mpa^1^‐Tyr^2^‐Phe^3^‐Gln^4^‐Asn^5^‐Cys^6^]‐Xaa^7^‐Arg^8^‐Gly^9^‐NH~2~ (Xaa = Sar [I] or MeAla [II]) were established using ROE and the ^3^J~HNHα~ couplings. Each of the peptides was found to exist in two stable isomers, pertaining to the cis or trans status of the Cys^6^‐Xaa^7^ peptide bond, thus giving rise to four study objects.

Two methods for studies of the conformational properties of the structures were compared. In the first, the algorithm consisted of three steps: (i) An Electrostatically Driven Monte‐Carlo (EDMC) search for low‐energy conformations. (ii) Simulations of the NOESY spectra and the vicinal couplings for these conformations. (iii) Determination of the statistical weights of the conformations with the ANALYZE package, so as to meet the best fit of the averaged NOE intensities and couplings to the experimental data. In the second method, the distance constraints and the torsion angles were used as the usual constraints in the Distance Geometry and Simulated Annealing algorithms. The flexibility of the pressin ring and the C‐terminus was characterized by a large number of families of conformations. The presence of the β‐turn at position 4,5 was confirmed for all low energy structures found. The use of the EDMC method for the elaboration of the NMR data for small flexible peptides yielded an adequate description of their conformational diversity and is the method of choice for the analysis of their solution structures. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd.