New tools for the control of peptide conformation: the helicogenic C-alpha-methyl, C alpha-cyclohexylglycine

The novel C-alpha-tetrasubstituted alpha-amino acid C-alpha-methyl, C-alpha-cyclohexylglycine was prepared by hydrogenation of its C-a-methyl, C-a-phenylglycine precursor. Terminally protected homodi-, homotri-, and homotetrapeptides from C-alpha-methyl, C-alpha-cyclohexylglycine and co-oligopeptides to the pentamer level in combination with Gly or alpha-aminoisobutyric acid residues were prepared by solution methods and fully characterized. The results of a conformational analysis, performed by use of Fourier transform infrared (FT-IR) spectrophotomet absorption, H-1 NMR, and X-ray diffraction techniques, support the contention that this C-alpha-methylated, C-beta-trisubstituted aliphatic alpha-amino acid is an effective beta-turn and 3(10)-helix inducer in tri- and longer peptides as its C-a-methyl valine parent compound, but partially divergent from the corresponding aromatic C-alpha-methyl, C-alpha-diphenylmethylglycine residue, known to promote folded and fully extended structures to a significant extent in these oligomers.