New tools for the control of peptide conformation: the helicogenic Calpha-methyl, Calpha-cyclohexylglycine.
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.
Formaggio
F
F
Institute of Biomolecular Chemistry, CNR, Department of Organic Chemistry, University of Padova, 35131 Padova, Italy. fernando.formaggio@unipd.it
Moretto
V
V
Crisma
M
M
Toniolo
C
C
Kaptein
B
B
Broxterman
Q B
QB
D000409:Alanine / Q000031:analogs & derivatives / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry; D018360:Crystallography, X-Ray; D005998:Glycine / Q000031:analogs & derivatives / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation
D000596:Amino Acids; C492092:C(alpha)-methyl-C(alpha)-cyclohexylglycine; D009842:Oligopeptides; D000409:Alanine; D005998:Glycine