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

:  The novel Cα-tetrasubstituted α-amino acid Cα-methyl, Cα-cyclohexylglycine was prepared by hydrogenation of its Cα-methyl, Cα-phenylglycine precursor. Terminally protected homodi-, homotri-, and homotetrapeptides from Cα-methyl, Cα-cyclohexylglycine and co-oligopeptides to the pentamer level in combination with Gly or α-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, 1H NMR, and X-ray diffraction techniques, support the contention that this Cα-methylated, Cβ-trisubstituted aliphatic α-amino acid is an effective β-turn and 310-helix inducer in tri- and longer peptides as its Cα-methyl valine parent compound, but partially divergent from the corresponding aromatic Cα-methyl, Cα-diphenylmethylglycine residue, known to promote folded and fully extended structures to a significant extent in these oligomers.