Helices in Peptides Containing Differentially Geminally Di-substituted Amino Acid Residues

We have explored the relative propensity of the three differentially di-substituted & gamma; amino acid residues, to be accommodated in all & alpha; helical conformations. We have established that small chiral hybrid peptides Boc-Aib-& gamma;(x,x)-Aib-Leu-Aib-Val-OMe (x,x=2,2/3,3/4,4) containing single geminally di-substituted & gamma; amino acid residue, can adopt both handedness of helical conformation in crystals and solution. The relative ease of being accommodated in helical structures decreased in the order & gamma;(4,4)>& gamma;(3,3)>& gamma;(2,2). & gamma;(4,4) and & gamma;(3,3) readily adopted C-12 helical conformations unlike & gamma;(2,2). & gamma;(2,2) and & gamma;(3,3) containing peptides, adopted either handedness of the helical conformation in crystals while in solution, they adopted right-handed helical conformation. Peptide, containing & gamma;(4,4) only adopted right-handed helical conformation both in the solid and solution states. Our studies established that position of di-substitution along the backbone of & gamma; amino acid residues determined their conformational preference, and thus might be used to generate diversity in the peptide conformations.