Conformation and Chiral Effects in α,β,α-Tripeptides

Short alpha,beta,alpha-tripeptides comprising a central chiral trisubstituted beta(2,2,3)*-amino acid residue form unusual gamma-turns and delta-turns in CDCl3 and DMSO-d(6) solutions but do not form beta-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 beta-amino acid residue within the triad. Accordingly, SSS tripeptides adopted an intraresidual gamma-turn like (C6) arrangement in the central beta-amino acid, whereas SRS diastereomers preferred an extended delta-turn (C9) conformation. A different SRS-stabilizing bias was observed in the crystal structures of the same compounds, which shared the extended delta-turn (C9) found in solution, but incorporated an additional extended beta-turn (C11) to form an overlapped double turn motif.