New tools for the control of peptide conformation: the helicogenic C^α‐methyl, C^α‐cyclohexylglycine*

Abstract

The novel Calpha-tetrasubstituted alpha-amino acid Calpha-methyl, Calpha-cyclohexylglycine was prepared by hydrogenation of its Calpha-methyl, Calpha-phenylglycine precursor. Terminally protected homodi-, homotri-, and homotetrapeptides from Calpha-methyl, Calpha-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) spectrophotometer absorption, 1H NMR, and X-ray diffraction techniques, support the contention that this Calpha-methylated, Cbeta-trisubstituted aliphatic alpha-amino acid is an effective beta-turn and 3(10)-helix inducer in tri- and longer peptides as its Calpha-methyl valine parent compound, but partially divergent from the corresponding aromatic Calpha-methyl, Calpha-diphenylmethylglycine residue, known to promote folded and fully extended structures to a significant extent in these oligomers.

Helical screw‐sense preferences of peptides based on chiral, Cα‐tetrasubstituted α‐amino acids

“…Additional examples of β‐branched, C α ‐tetrasubstituted α‐amino acids are (αMe)Chg and (αMe)Phg (Figure ). The X‐ray diffraction structure of the right‐handed helical tetrapeptide Z‐(Aib) 2 ‐ l ‐(αMe)Chg‐Aib‐O t Bu suggests that the relationship between α‐carbon configuration and helix screw sense found for (αMe)Val holds for (αMe)Chg as well, even if the β‐branching is included in a cycloaliphatic ring. Conversely, in (αMe)Phg the C β and the two C γ atoms are part of a phenyl ring.…”

Handedness preference and switching of peptide helices. Part II: Helices based on noncodedα‐amino acids

“…In the last part of this section, we will treat and classify the large body of available literature data on the control of the screw sense of achiral, Aib‐rich, β ‐turn, incipient or fully developed 3 10 ‐helical (depending on peptide main‐chain length) host sequences induced by one (or two contiguous) chiral, either C α ‐tri‐ or C α ‐tetrasubstituted α ‐amino acid(s). The discussion will be first focused on the case where the interpretation of the results is the most straightforward, namely, when the localization of the guest residue(s) is in an internal position of the sequence . Here, a single C α ‐alkylated α ‐amino acid guest (e.g.…”