Conformational studies on model dipeptides of Gly,L -Ala and their Cα-substituted analogs

As a part of the development of conformational guidelines for the design of metabolically altered peptidomimetics, we present conformational energy calculations on model dipeptide compounds with glycine (Gly), L-alanine (Ala), α-aminoisobutyric acid (Aib), L-tert-butylglycine (Tle), L-phenylglycine (Phg), (α,α)-diphenylglycine (Dφg), L-2-aminobutyric acid (Abu), 2-amino-2-ethylbutync acid (Deg), L-2-amino-2-vinylacetic acid (Ava) and (α,α)-divinylglycine (Dvg). The energy calculations have been made using molecular mechanics methods with a force field derived from MM2. The salient features are expressed in terms of conformational energy plots, drawn as a function of the backbone torsion angles φ(C_i-1′-N_i-C_i^α-C_i′) and ψ(N_i- C_i^α-N_{i + 1}). The low-energy structures of these compounds are qualitatively consistent with the X-ray crystal structure analyses of peptides and peptidomimetics. They are also in agreement with the results of the solution-phase studies carried out by NMR and IR techniques. The results obtained have important implications in the design of conformationally restricted peptidomimetics.