Preferred conformation of peptides rich in Ac8c, a medium-ring alicyclic C (alpha,alpha)-disubstituted glycine

J Pept Sci. 1996 Jan-Feb;2(1):14-27. doi: 10.1002/psc.43.

Abstract

A complete series of terminally blocked, monodispersed homo-oligopeptides (to the pentamer level) from the sterically demanding, medium-ring alicyclic C (alpha,alpha)-disubstituted glycine 1-aminocyclooctane-1-carboxylic acid (Ac8c), and two Ala/Ac8c tripeptides, were synthesized by solution methods and fully characterized. The preferred conformation of all the oligopeptides was determined in deuterochloroform solution by IR absorption and 1H-NMR. The molecular structures of the amino acid derivative Z-Ac8c-OH, the dipeptide pBrBz-(Ac8c)2-OH and the tripeptide pBrBz-(Ac8c)3-OtBu were assessed in the crystal state by X-ray diffraction. Conformational energy computations were performed on the monopeptide Ac-Ac8c-NHMe. Taken together, the results obtained strongly support the view that the Ac8c residue is an effective beta-turn and helix former. A comparison is also made with the conformational preferences of alpha-aminoisobutyric acid, the prototype of C (alpha,alpha)-disubstituted glycines, and of the other members of the family of 1-aminocycloalkane-1-carboxylic acids (Acnc with n = 3, 5-7) investigated so far. The implications for the use of the Ac8c residue in peptide conformational design are considered.

MeSH terms

  • Amino Acids / chemistry*
  • Amino Acids, Cyclic*
  • Glycine / analogs & derivatives*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Peptides / chemistry*
  • Protein Conformation*
  • Spectroscopy, Fourier Transform Infrared
  • X-Ray Diffraction
  • gamma-Aminobutyric Acid / chemistry

Substances

  • Amino Acids
  • Amino Acids, Cyclic
  • Peptides
  • 1-aminocyclooctanecarboxylic acid
  • gamma-Aminobutyric Acid
  • Glycine