Conformational analysis of small peptides of the type Ac–X–NHMe, where X=Gly, Ala, Aib and Cage

Abstract

This is the second paper which reports the results obtained from a systematic conformational analysis of the (R)-8-amino-pentacyclo[5.4.0.0 2,6.0 3,10.0 5,9]undecane-8-carboxylic acid monopeptide (Cage monopeptide), using molecular mechanics and ab initio methods. The purpose of this paper is to highlight the performance of force field calculations of a series of amino acids with the ab initio calculations. The series of amino acids, Gly, Ala, Aib and Cage, exhibit a decrease of the conformational space upon an increase of steric factors due to an increase in substitution at the α-carbon. The Ramachandran maps computed in vacuo using the different parameterizations of the Parm94 and Parm96 AMBER force fields, which are not explicitly parameterized for the Cage amino acid, compares favourably with the ab initio results performed at the HF level using the 6-31G* basis set. Analysis of these maps reveal the helical-conformational preferences of the Cage monopeptide, which has the potential to be incorporated in the design of constrained cyclic peptide analogues.