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

The tendency to adopt β-turn conformation by model dipeptides with α,β-dehydrophenylalanine (ΔPhe) 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 β-turn stability. An extensive computational study of the conformational preferences of Z and E isomers of dipeptides Ac-Gly-(E/Z)-ΔPhe-NHMe (1a / 1b) and Ac-Gly-(E/Z)-ΔPhe-NMe(2) (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)-ΔPhe-NHMe has a great tendency to adopt β-turn conformation. In the gas phase the type II β-turn is preferred, whereas in the polar environment, the type I. On the other hand, dehydro residue in Ac-Gly-(E)-ΔPhe-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 β-turn conformations is much weaker for the N-methylated Z isomer (Ac-Gly-(Z)-ΔPhe-NMe(2) ), both in vacuo and in the polar environment. On the contrary, N-methylated E isomer (Ac-Gly-(E)-ΔPhe-NMe(2) ) can easier adopt β-turn conformation, but the backbone torsion angles (ϕ(1) , ψ(1) , ϕ(2) , ψ(2) ) are off the limits for common β-turn types.