Psi[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 a-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(CF3)NH]Glytetrapeptides 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 b turn structures for all the L-peptides; on the other hand, a D-stereochemistry at the Pro residue induces a natural folding towards a b hairpin conformation driven by the formation of a second hydrogen bond, regardless of the stereochemistry of the stereogenic peptide bond surrogate.
Psi[CH(CF3)NH]Gly-peptides: Synthesis and Conformation Analysis
VOLONTERIO, ALESSANDRO;
2009-01-01
Abstract
Psi[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 a-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(CF3)NH]Glytetrapeptides 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 b turn structures for all the L-peptides; on the other hand, a D-stereochemistry at the Pro residue induces a natural folding towards a b hairpin conformation driven by the formation of a second hydrogen bond, regardless of the stereochemistry of the stereogenic peptide bond surrogate.File | Dimensione | Formato | |
---|---|---|---|
Org. Biomol. Chem. 2009, 2286-2296.pdf
Accesso riservato
:
Altro materiale allegato
Dimensione
493.08 kB
Formato
Adobe PDF
|
493.08 kB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.