Structural versatility of peptides from Cα, α‐disubstituted glycines: Crystal‐state conformational analysis of homopeptides from Cα‐methyl, Cα‐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, Cα, α‐disubstituted glycine Cα‐methyl, Cα‐benzylglycine [(αMe)Phe], have been determined by x‐ray diffraction. The derivative is mClAc‐D‐(αMe)Phe‐OH, and the peptides are pBrBz‐[D‐(αMe)Phe]2‐NHMe, pBrBz‐[D‐(αMe)Phe]3‐OH hemihydrate, and pBrBz‐[D‐(αMe)Phe]4‐OtBu 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 CO…︁HN intramolecular H bond. The structure of the tripeptide carboxylic acid is further stabilized by a 1 ← 4 CO…︁HO intramolecular H bond, forming an “oxy‐analogue” of a β‐turn. The tetrapeptide ester is folded in a regular (incipient) 310‐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 Cα‐methylated α‐amino acids.