The conformational properties of dehydrobutyrine and dehydrovaline: theoretical and solid-state conformational studies

Dehydrobutyrine is the most naturally occurring dehydroamino acid. It is also the simplest dehydroamino acid having the geometrical isomers EIZ. To investigate its conformational properties, a theoretical analysis was performed on N-acetyl-alpha,beta-dehydrobutyrine N'-methylamides, Ac-(E)-Delta Abu-NHMe and Ac-(Z)-Delta Abu-NHMe, as well as the dehydrovaline derivative Ac-Delta Val-NHMe. The phi, psi potential energy surfaces and the localised conformers were calculated at the B3LYP/6-311++G(d,p) level of theory both in vacuo and with inclusion of the solvent (chloroform, water) effect (SCRF method). The X-ray crystal structures of Ac-(Z)-Delta Abu-NHMe and Ac-Delta Val-NHMe were determined at 85 and 100 K, respectively. The solid-state conformational preferences for the studied residues have been analysed and compared with the other related structures. Despite the limitations imposed by the C-alpha = C-beta double bond on the topography of the side chains, the main chains of the studied dehydroamino acids are more flexible than in standard alanine. The studied dehydroamino acids differ in their conformational preferences, which depend on the polarity of the environment. This might be a reason why the nature quite precisely differentiates between Delta Val and each of the Delta Abu isomers, and why, particularly so with the latter, they are used as a conformational tool to influence the biological action of usually small, cyclic dehydropeptides. Copyright (c) 2010 European Peptide Society and John Wiley & Sons, Ltd.