Psi[CH(CF(3))NH]Gly-peptides: synthesis and conformation analysis

Org Biomol Chem. 2009 Jun 7;7(11):2286-96. doi: 10.1039/b901718f. Epub 2009 Apr 7.

Abstract

Psi[CH(CF(3))NH]Gly peptides, a conceptually new class of peptidomimetics having a stereogenic trifluoroethylamine group as a natural peptide-bond surrogate, have been synthesized by stereoselective addition of alpha-amino acid esters to trans-3,3,3-trifluoro-1-nitropropene. Long range nuclear Overhauser effects, detected via ROESY experiments, provided evidence that model Psi[CH(CF(3))NH]Gly-tetrapeptides incorporating a trifluoroethylamine mimic of the dipeptide loop Pro-Gly can be represented by an ensemble of unfolded and folded conformations. The latter are driven by the formation of a hydrogen bond between a carbonyl group and the aminic proton of the trifluoroethylamine unit. MD calculations indicate a population of conformers which adopt folded beta turn structures for all the L-peptides; on the other hand, a D-stereochemistry at the Pro residue induces a natural folding towards a beta hairpin conformation driven by the formation of a second hydrogen bond, regardless of the stereochemistry of the stereogenic peptide bond surrogate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomimetics
  • Computer Simulation
  • Ethylamines / chemical synthesis
  • Ethylamines / chemistry*
  • Hydrogen Bonding
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Protein Conformation
  • Protein Structure, Secondary
  • Stereoisomerism

Substances

  • Ethylamines
  • Peptides
  • trifluoroethylamine