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 language | English |
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Pages (from-to) | 2286-2296 |
Number of pages | 11 |
Journal | Organic & Biomolecular Chemistry |
Volume | 7 |
Issue number | 11 |
Early online date | 7 Apr 2009 |
DOIs | |
Publication status | Published - 7 Jun 2009 |
Keywords
- biomimetics
- computer simulation
- ethylamines
- hydrogen bonding
- models, molecular
- nuclear magnetic resonance, biomolecular
- peptides
- protein conformation
- protein structure, secondary
- stereoisomerism