Conformational properties of N-acetyl-N-methyl-α,β-dehydroalanine N-methylamide

The conformational properties of Ac-Δ(Me)Ala-NHMe (N-acetyl-N-methyl-α,β-dehydroalanine N'-methylamide), as the simplest model of N-methyl-α,β-dehydroamino acids, was examined with theoretical methods and in comparison with Ac-ΔAla-NHMe and Ac-ΔAla-NMe2. The N-terminal amide of the Δ(Me)Ala residue easily adopts the configuration cis and the torsion angles φ, ψ are highly flexible. The Δ(Me)Ala residue is a conformational flexibilizer as compared to the parent ΔAla, which is a conformational stiffener. This seems to be the reason why Δ(Me)Ala is found in small natural cyclic peptides, where it ensures the conformational flexibility necessary for biological action.