Conformational interconversions in peptide β-turns: Discrimination between enantiomeric conformations by chiral perturbation

Abstract

The crystal structure of the model tripeptide Boc-Aib-Gly-Leu-OMe (1) reveals two independent molecules in the asymmetric unit that adopt ‘‘enantiomeric’’ type I and type I’ beta-turn conformations with the Aib and Gly residues occupying the corner ( i / 1 and I / 2) positions. 13C cross polarization and magic angle sample spinning spectra in the solid state also support the coexistence of two conformational species. 13C-nmr in CDCl3 establishes the presence of a single species or rapid exchange between conformations. 400 MHz 1H-nmr provides evidence for conformational exchange involving a major and minor species, with beta-turn conformations supported by the low solvent exposure of Leu(3) NH and the observation of NiH - Ni/1H nuclear Overhauser effects. CD bands in the region 190–230 nm are positive, supporting a major population of type I’ beta-turns. The isomeric peptide, Boc-Gly-Leu-Aib-Ome (2) , adopts an ‘‘open’’ type II’ b-turn conformation in crystals. Solid state and solution nmr support population of a single conformational species. Chiral perturbation introduced outside the folded region of peptides may provide a means of modulating screw sense in achiral sequences.