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

Abstract : The molecular and crystal structures of one derivative and three homopeptides (from the di-to the tetrapeptide level) of the chiral, C"*"-disubstituted glycine C"-methyl, C"-benzylglycine [ (aMe) Phe] , have been determined by x-ray diffraction. The derivative is mClAc-D-(aMe) Phe-OH, and the peptides are pBrBz-[ D-(aMe) PheI2-NHMe, pBrBz-[ D-(aMe) PheI3-OH hemihydrate, and pBrBz-[ D-(aMe) PheI4-OtBu sesquihydrate. All (aMe) Phe residues prefer 4,# torsion angles in the helical region of the conformational map. The dipeptide methylamide and the tripeptide carboxylic acid adopt a &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 6 4 C =O-*-H-0 intramolecular H bond, forming an "oxy-analogue" of a @-turn. The tetrapeptide ester is folded in a regular (incipient) 310-helix. In general, the relationship between (aMe) 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"-methylated a-amino acids.