Structural versatility of peptides from C α, α ‐disubstituted glycines: Crystal‐state conformational analysis of homopeptides from C α ‐methyl, C α ‐benzylglycine [(αMe)Phe] n

The molecular and crystal structures of one derivative and three homopeptides (from the di‐to the tetrapeptide level) of the chiral, C α, α ‐disubstituted glycine C α ‐methyl, C α ‐benzylglycine [(αMe)Phe], have been determined by x‐ray diffraction. The derivative is mClAc‐ D ‐(αMe)Phe‐OH, and the peptides are p BrBz‐[ D ‐(αMe)Phe] 2 ‐NHMe, p BrBz‐[ D ‐(αMe)Phe] 3 ‐OH hemihydrate, and p BrBz‐[ D ‐(αMe)Phe] 4 ‐O t Bu sesquihydrate. All (αMe)Phe residues prefer ϕ,ψ torsion angles in the helical region of the conformational map. The dipeptide methylamide and the tripeptide carboxylic acid adopt a β‐turn conformation with a 1 ← 4 CO…HN intramolecular H bond. The structure of the tripeptide carboxylic acid is further stabilized by a 1 ← 4 CO…HO intramolecular H bond, forming an “oxy‐analogue” of a β‐turn. The tetrapeptide ester is folded in a regular (incipient) 3 10 ‐helix. In general, the relationship between (αMe)Phe chirality and helix screw sense is opposite to that exhibited by protein amino acids. A comparison is made with the conclusions extracted from published work on homopeptides from other C α ‐methylated α‐amino acids. © 1993 John Wiley & Sons, Inc.