title: Folding of peptides characterized by c3Val, a highly constrained analogue of valine.
abstract: Using a combined chemical/chiral chromatographic approach we synthesized an N-protected derivative of (R)-c(3)Val, a severely conformationally restricted C(alpha)-tetrasubstituted alpha-amino acid characterized by a C(beta,beta)-dimethylated cyclopropane system. A set of terminally protected derivatives and model peptides (to the heptamer level), containing one or two (R)-c(3)Val residues in combination with either Aib or Gly residues, was prepared by solution methods. A detailed solution and crystal-state conformational investigation, based on Fourier transform infrared (FTIR) absorption, (1)H-NMR, and x-ray diffraction techniques, performed in comparison with a similar study on related derivatives and peptides rich in (alphaMe)Val, the prototype of C(alpha)-tetrasubstituted alpha-amino acids of this subfamily, allowed us to conclude the following: (a) c(3)Val is a good beta-bend and helix former, although less efficient than (alphaMe)Val. (b) The relationship between alpha-carbon chirality and screw sense of the folded structure formed is the same as that of (alphaMe)Val, i.e., the (R)-enantiomer has a strong left-handed bias. (c) c(3)Val seems more prone than (alphaMe)Val to fold into a gamma-bend conformation. The conformational propensities of C(beta,beta)-disubstituted Ac(3)c residues are also discussed in comparison with those of the parent cyclopropane residue.
authors.affiliation: Institute of Biomolecular Chemistry, CNR, Department of Organic Chemistry, University of Padova, 35131 Padova, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Peggion
authors.forename: Fernando
authors.initials: F
authors.lastname: Formaggio
authors.forename: Marco
authors.initials: M
authors.lastname: Crisma
authors.forename: Claudio
authors.initials: C
authors.lastname: Toniolo
authors.forename: Ana I
authors.initials: AI
authors.lastname: Jiménez
authors.forename: Carlos
authors.initials: C
authors.lastname: Cativiela
authors.forename: Bernard
authors.initials: B
authors.lastname: Kaptein
authors.forename: Quirinus B
authors.initials: QB
authors.lastname: Broxterman
authors.forename: Michele
authors.initials: M
authors.lastname: Saviano
authors.forename: Ettore
authors.initials: E
authors.lastname: Benedetti
mesh_terms: D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008968:Molecular Conformation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D014633:Valine / Q000031:analogs & derivatives* / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D009842:Oligopeptides; D010455:Peptides; D014633:Valine