Conformation and chiral effects in α,β,α-tripeptides

Abstract

Short α,β,α-tripeptides comprising a central chiral trisubstituted β 2,2,3*-amino acid residue form unusual γ-turns and δ-turns in CDCl 3 and DMSO-d 6 solutions but do not form β-turns. Thermal coefficients of backbone amide protons, 2D-NMR spectra, and molecular modeling revealed that these motifs were strongly dependent on the configuration (chiral effect) of the central β-amino acid residue within the triad. Accordingly, SSS tripeptides adopted an intraresidual γ-turn like (C6) arrangement in the central β-amino acid, whereas SRS diastereomers preferred an extended δ-turn (C9) conformation. A different SRS-stabilizing bias was observed in the crystal structures of the same compounds, which shared the extended δ-turn (C9) found in solution, but incorporated an additional extended β-turn (C11) to form an overlapped double turn motif.