Molecular mechanics studies on dipeptide models of diphenylalanine and its derivatives.

Abstract

As a part of our studies on the structure and conformations of peptidomimetics, we present conformational energy calculations on model peptides with (a) diphenyl alanine and its tricyclic derivatives and (b) triphenyl alanine residues using molecular mechanics and conformational analysis methods. The energies are calculated as a function of the backbone torsions (phi and psi), and the results are presented in terms of isoenergy contours in the phi-psi space. The low-energy models adopt conformations characteristic of a variety of regular structures such as the alpha-helix, gamma-turn and polyproline-II-type three- and four-fold helices. The conformational preferences in the model peptides with diphenyl alanine and its tricyclic derivatives are sensitive to the side-chain torsion, with some similarities to the corresponding preferences of L-Ala dipeptide. The energy profile of the model peptide with triphenyl alanine is similar to that of the model peptide with Tle (tert-leucine) residue. The results of our studies have implications in the design of conformationally constrained peptidomimetics with structures in the beta- and alpha-helical regions.