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

• Published in: Journal of organic chemistry 2012-07, Vol.77 (14), p.5907-5913
• Main Authors: Saavedra, Carlos J, Boto, Alicia, Hernández, Rosendo, Miranda, José Ignacio, Aizpurua, Jesus M
• Format: Article
• Language: English
• Subjects: Carbohydrate Conformation; Chemistry; Crystallography, X-Ray; Exact sciences and technology; Models, Molecular; Oligopeptides - chemical synthesis; Oligopeptides - chemistry; Organic chemistry; Peptides; Preparations and properties
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo300892u

Short α,β,α-tripeptides comprising a central chiral trisubstituted β2,2,3*-amino acid residue form unusual γ-turns and δ-turns in CDCl3 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.