STRUCTURAL VERSATILITY OF PEPTIDES FROM C-ALPHA,C-ALPHA-DISUBSTITUTEDGLYCINES - 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 pe ptides 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 M e)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 intramolecul ar 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 e xtracted from published work on peptides from other types of C-alpha-a lkylated aromatic alpha-amino acids. (C) Munksgaard 1996.