Helical Screw-Sense Preferences of Peptides Based on Chiral, C-alpha-Tetrasubstituted alpha-Amino Acids

The preferred helical screw senses of chiral alpha-amino acids with a C-alpha-tetrasubstituted alpha-carbon atom, as determined in the crystal state by X-ray diffraction analyses on derivatives and peptides, are reviewed. This survey covers C-alpha-methylated and C-alpha-ethylated -amino acids, as well as alpha-amino acids cyclized on the alpha-carbon, including those characterized by the combination of lack of chirality at the alpha-carbon with either side-chain or axial chirality. Although, in general, chiral C-alpha-tetrasubstituted -amino acids show a less pronounced bias toward a single helical screw sense than their proteinogenic (C-alpha-trisubstituted) counterparts, our analysis highlights significant differences in terms of magnitude and direction of such a bias among the various sub-families of residues, and between individual amino acids within each sub-family as well. The experimental findings can be rationalized, at least in part, on the basis of steric considerations. (c) 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 46-64, 2015.