Ψ[CH(CF3)NH]Gly-peptides

synthesis and conformation analysis

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

Research output: Contribution to journalArticle

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

Fingerprint

peptides
Conformations
Stereochemistry
methylidyne
Peptides
Hydrogen
prolylglycine
Hydrogen bonds
stereochemistry
synthesis
Peptidomimetics
Dipeptides
hydrogen bonds
Overhauser effect
Protons
Esters
folding
amino acids
Amino Acids
esters

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

Ψ[CH(CF3)NH]Gly-peptides : synthesis and conformation analysis. / Molteni, Marco; Bellucci, Maria Cristina; Bigotti, Serena; Mazzini, Stefania; Volonterio, Alessandro; Zanda, Matteo.

In: Organic & Biomolecular Chemistry, Vol. 7, No. 11, 07.06.2009, p. 2286-2296.

Research output: Contribution to journalArticle

Molteni, M, Bellucci, MC, Bigotti, S, Mazzini, S, Volonterio, A & Zanda, M 2009, 'Ψ[CH(CF3)NH]Gly-peptides: synthesis and conformation analysis', Organic & Biomolecular Chemistry, vol. 7, no. 11, pp. 2286-2296. https://doi.org/10.1039/b901718f
Molteni M, Bellucci MC, Bigotti S, Mazzini S, Volonterio A, Zanda M. Ψ[CH(CF3)NH]Gly-peptides: synthesis and conformation analysis. Organic & Biomolecular Chemistry. 2009 Jun 7;7(11):2286-2296. https://doi.org/10.1039/b901718f
Molteni, Marco ; Bellucci, Maria Cristina ; Bigotti, Serena ; Mazzini, Stefania ; Volonterio, Alessandro ; Zanda, Matteo. / Ψ[CH(CF3)NH]Gly-peptides : synthesis and conformation analysis. In: Organic & Biomolecular Chemistry. 2009 ; Vol. 7, No. 11. pp. 2286-2296.
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AB - 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.

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