β-turn tendency in N-methylated peptides with dehydrophenylalanine residue: DFT study

The tendency to adopt beta-turn conformation by model dipeptides with a,beta-dehydrophenylalanine (?Phe) residue in the gas phase and in solution is investigated by theoretical methods. We pay special attention to a dependence of conformational properties on the side-chain configuration of dehydro residue and the influence of N-methylation on beta-turn stability. An extensive computational study of the conformational preferences of Z and E isomers of dipeptides Ac-Gly-(E/Z)-?Phe-NHMe (1a / 1b) and Ac-Gly-(E/Z)-?Phe-NMe2 (2a/2b) by B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) methods is reported. It is shown that, in agreement with experimental data, Ac-Gly-(Z)-?Phe-NHMe has a great tendency to adopt beta-turn conformation. In the gas phase the type II beta-turn is preferred, whereas in the polar environment, the type I. On the other hand, dehydro residue in Ac-Gly-(E)-?Phe-NHMe has a preference to adopt extended conformations in all environments. N-methylation of C-terminal amide group, which prevents the formation of 1?4 intramolecular hydrogen bond, change dramatically the conformational properties of studied dehydropeptides. Especially, the tendency to adopt beta-turn conformations is much weaker for the N-methylated Z isomer (Ac-Gly-(Z)-?Phe-NMe2), both in vacuo and in the polar environment. On the contrary, N-methylated E isomer (Ac-Gly-(E)-?Phe-NMe2) can easier adopt beta-turn conformation, but the backbone torsion angles (?1, ?1, ?2, ?2) are off the limits for common beta-turn types. (c) 2012 Wiley Periodicals, Inc. Biopolymers 97:518528, 2012.