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Folding of peptides characterized by c 3 Val, a highly constrained analogue of valine
Author(s) -
Peggion Cristina,
Formaggio Fernando,
Crisma Marco,
Toniolo Claudio,
Jiménez Ana I.,
Cativiela Carlos,
Kaptein Bernard,
Broxterman Quirinus B.,
Saviano Michele,
Benedetti Ettore
Publication year - 2003
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.10295
Subject(s) - chemistry , cyclopropane , folding (dsp implementation) , stereochemistry , enantiomer , residue (chemistry) , chirality (physics) , amino acid , peptide , chemical shift , crystallography , organic chemistry , ring (chemistry) , chiral symmetry , biochemistry , nambu–jona lasinio model , physics , quantum mechanics , quark , electrical engineering , engineering
Using a combined chemical/chiral chromatographic approach we synthesized an N‐protected derivative of (R)–c 3 Val, a severely conformationally restricted C α ‐tetrasubstituted α‐amino acid characterized by a C β,β ‐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 (αMe)Val, the prototype of C α ‐tetrasubstituted α‐amino acids of this subfamily, allowed us to conclude the following: (a) c 3 Val is a good β‐bend and helix former, although less efficient than (αMe)Val. (b) The relationship between α‐carbon chirality and screw sense of the folded structure formed is the same as that of (αMe)Val, i.e., the (R)‐enantiomer has a strong left‐handed bias. (c) c 3 Val seems more prone than (αMe)Val to fold into a γ‐bend conformation. The conformational propensities of C β,β ‐disubstituted Ac 3 c residues are also discussed in comparison with those of the parent cyclopropane residue. © 2002 Wiley Periodicals, Inc. Biopolymers 68: 178–191, 2003