Helices in Peptides Containing Differentially Geminally Di‐substituted γ Amino Acid Residues

Abstract

AbstractWe have explored the relative propensity of the three differentially di‐substituted γ amino acid residues, to be accommodated in all α helical conformations. We have established that small chiral hybrid peptides Boc‐Aib‐γx,x‐Aib‐Leu‐Aib‐Val‐OMe (x,x=2,2/3,3/4,4) containing single geminally di‐substituted γ 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 γ4,4>γ3,3>γ2,2. γ4,4 and γ3,3 readily adopted C12 helical conformations unlike γ2,2. γ2,2 and γ3,3 containing peptides, adopted either handedness of the helical conformation in crystals while in solution, they adopted right‐handed helical conformation. Peptide, containing γ4,4 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 γ amino acid residues determined their conformational preference, and thus might be used to generate diversity in the peptide conformations.