Conformation of Achiral alpha/beta Hybrid Peptides Containing Glycine and 1-Aminocyclohexaneacetic Acid

The present work describes the conformation of achiral alpha/beta hybrid peptides, Boc-Gly-beta(3,3)-Ac(6)c-NHMe (P1), Boc-Gly-beta(3,3)-Ac(6)c-Gly-OMe (P2), and Boc-Gly-beta(3,3)-Ac(6)c-Gly-beta(3,3)-Ac(6)c-OMe, (P3) using X-ray crystallography. Peptides P1 and P2 adopt C-11 and C-12 folded conformations, respectively. The directionality of the hydrogen bond observed in P1 is opposite to that observed in peptide P2. In case of tetrapeptide P3, no such hydrogen bond is observed. Further, the solvent titration experiment establishes the similar intramolecular hydrogen bonding as observed in the crystals. In P1 and P2, the amino group of beta(3,3)-Ac(6)c occupies equatorial orientations, while in the case of peptide P3, it occupies axial and equatorial orientations for residues beta(3,3)-Ac(6)c(2) and beta(3,3)-Ac(6)c(4), respectively. The average (phi,theta,psi) torsional preferences of beta(3,3)-Ac(6)c in achiral alpha/beta peptides are somewhat different from that of chiral alpha/beta peptides.