Computational study of the conformational preferences of the (R)-8-amino-pentacyclo(5.4-0.02,6.03,10.05,9) undecane-8-carboxylic acid monopeptide

alpha-Amino acids are important building blocks for the synthesis of a large number of bioactive compounds and pharmaceutical drugs. However, a literature survey revealed that no theoretical conformational study of a-amino acids with cage carbon frameworks has been performed to date. This paper reports the results of a conformational study on 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 in vacuo, Ramachandran maps computed using the different parameterizations of the AMBER force field show the C-7eq structure as the most favourable conformation, in contrast to the C-7ax structure, that is the lowest energy conformation at the ab initio level. Analysis of these maps reveals the helical preference for the monopeptide and provides the potential for the cage residue to be incorporated into constrained peptide analogues. Copyright (C) 2003 European Peptide Society and John Wiley Sons, Ltd.