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. © 2012 Wiley Periodicals, Inc. Biopolymers 97:518–528, 2012.