Ψ[CH(CF3)NH]Gly-peptides: synthesis and conformation analysis

Marco Molteni, Maria Cristina Bellucci, Serena Bigotti, Stefania Mazzini, Alessandro Volonterio, Matteo Zanda

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34 Citations (Scopus)

Abstract

Ψ[CH(CF3)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 α-amino acid esters to trans-3,3,3-trifluoro-1-nitropropene. Long range nuclear Overhauser effects, detected viaROESY experiments, provided evidence that model Ψ[CH(CF3)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 β turn structures for all the L-peptides; on the other hand, a D-stereochemistry at the Pro residue induces a natural folding towards a β hairpin conformation driven by the formation of a second hydrogen bond, regardless of the stereochemistry of the stereogenic peptide bond surrogate.
Original languageEnglish
Pages (from-to)2286-2296
Number of pages11
JournalOrganic & Biomolecular Chemistry
Volume7
Issue number11
Early online date7 Apr 2009
DOIs
Publication statusPublished - 7 Jun 2009

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Keywords

  • biomimetics
  • computer simulation
  • ethylamines
  • hydrogen bonding
  • models, molecular
  • nuclear magnetic resonance, biomolecular
  • peptides
  • protein conformation
  • protein structure, secondary
  • stereoisomerism

Cite this

Molteni, M., Bellucci, M. C., Bigotti, S., Mazzini, S., Volonterio, A., & Zanda, M. (2009). Ψ[CH(CF3)NH]Gly-peptides: synthesis and conformation analysis. Organic & Biomolecular Chemistry, 7(11), 2286-2296. https://doi.org/10.1039/b901718f