Structural versatility of peptides from Cα,α-disubstituted glycines: crystal-state conformational analysis of peptides from Cα-methylhomophenylalanine, (αMe)Hph

Abstract
The molecular and crystal structures of the Cα‐tetrasubstituted, δ‐branched α‐amino acid Cα‐methyl‐homophenylalanine, H‐d‐(αMe)Hph‐OH, and three peptides (to the pentamer level), including the homotripeptide, have been determined by X‐ray diffraction. The peptides are Z‐l‐(αMe)Hph‐(l‐Ala)2‐OMe, pBrBz‐[d‐(αMe)Hph]3‐OtBu and Ac‐(Aib)2‐l‐(αMe)Hph‐(Aib)2‐OtBu. All the (αMe)Hph residues prefer φ,ψ torsion angles in the helical region of the conformational map. The two terminally blocked tripeptides adopt a β‐bend conformation stabilized by a 1→4 C = O⋯H‐N intramolecular H‐bond. The terminally blocked pentapeptide is folded in a regular 310‐helix. In general, the relationship between (αMe)Hph α‐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 Cα‐alkylated aromatic α‐amino acids. © Munksgaard 1996.

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