(alphaMe)Nva: stereoselective syntheses and preferred conformations of selected model peptides

J Pept Res. 2000 Nov;56(5):283-97. doi: 10.1034/j.1399-3011.2000.00768.x.

Abstract

Using different stereoselective chemical and chemoenzymatic approaches we synthesized the chiral, Calpha-methylated alpha-amino acid L-(alphaMe)Nva with a short, linear side-chain. A set of terminally protected model peptides to the pentamer level containing either (alphaMe)Nva or Nva in combination with Ala and/or Aib was prepared using solution methods and characterized fully. Two (alphaMe)Nva peptides were also synthesized using side-chain hydrogenation of the corresponding Calpha-methyl, Calpha-allylglycine (Mag) peptides. A detailed solution and crystal-state conformational analysis based on FT-IR absorption, 1H NMR and X-ray diffraction techniques allowed us to define that: (i) (alphaMe)Nva is an effective beta-turn and 3(10)-helix former; and (ii) the relationship between (alphaMe)Nva chirality and the screw sense of the turn/helix formed is that typical of protein amino acids, i.e. L-(alphaMe)Nva induces the preferential formation of right-handed folded structures. In more general terms, this study reinforced previous conclusions that peptides based on alpha-amino acids with a Calpha-methyl substituent and a Calpha-linear alkyl substituent are characterized by a strong tendency to fold into turn and helical structures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallization
  • Cyclic N-Oxides
  • Hydrogen Bonding
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry*
  • Protein Folding
  • Protein Structure, Secondary
  • Solutions
  • Spectroscopy, Fourier Transform Infrared
  • Stereoisomerism
  • Valine / analogs & derivatives*
  • Valine / chemical synthesis
  • Valine / chemistry
  • X-Ray Diffraction

Substances

  • Cyclic N-Oxides
  • Oligopeptides
  • Solutions
  • 2-methylnorvaline
  • Valine
  • TEMPO