Structural versatility of peptides from C-alpha,C-alpha-disubstituted glycines: Crystal-state conformational analysis of peptides from C-alpha-methylhomophenylalanine, (alpha Me)Hph

The molecular and crystal structures of the C-alpha-tetrasubstituted, delta-branched alpha-amino acid C-alpha-methylhomophenylalanine, H-D-(alpha Me)Hph-OH, and three peptides (to the pentamer level), including the homotripeptide, have been determined by X-ray diffraction. The peptides are Z-L-(alpha Me)Hph-(L-Ala)(2)-OMe, pBrBz-[D-(alpha Me)Hph](3)-OtBu and Ac-(Aib)(2)-L-(alpha Me)Hph-(Aib)(2)-OtBu. All the (alpha Me)Hph residues prefer phi,psi torsion angles in the helical region of the conformational map. The two terminally blocked tripeptides adopt a beta-bend conformation stabilized by a 1<--4 C=O ... H-N intramolecular H-bond. The terminally blocked pentapeptide is folded in a regular 3(10)-helix. In general, the relationship between (alpha Me)Hph alpha-carbon chirality and helix handedness is the same as that exhibited by protein amino acids. A comparison is also made with the conclusions extracted from published work on peptides from other types of C-alpha-alkylated aromatic alpha-amino acids. (C) Munksgaard 1996.