Conformational preference of azaglycine-containing dipeptides studied by PCM and IPCM methods

Abstract

The minimum energy conformations for azaglycine-containing dipeptides, Ac-Ala-azaGly-NH2 (I) and Ac-Phe-azaGly-NH2 (II) were calculated at the HF/6-31G* level of theory by applying the polarizable continuum model (PCM) and the isodensity polarizable continuum model (IPCM) to investigate solvent effect on conformational stability. The most stable conformers calculated by two solvation methods were confirmed experimentally to evaluate which of solvation models is more reliable. A wide range of conformers was searched in the HF/6-31G* structures for azapeptide I. The conformers less than 5 kcal/mol in relative energy were selected as minima of I, and minima of azapeptide II were generated at the HF/6-31G* level based on the backbone geometries for minima of I. The relative energies of stable conformers and the global minima for I and II in DMSO solvent depend significantly on solvation methods. To characterize these inconsistencies in solvation models, the solution conformations of H were examined with NMR spectroscopy and the restricted molecular dynamics in conjunction with the ab initio method. The solution conformation of II by NMR spectroscopy is determined to adopt a betaII-turn(major) or betaI-turn(minor) structures as predicted by IPCM method. These theoretical and experimental results indicate that IPCM is more reliable than PCM in prediction of the conformational preference for azapeptide in DMSO solution structures. (C) 2003 Elsevier B.V. All rights reserved.