α,β2,3 -Disteroisomeric foldamers of general formula Boc(S-Ala-β-2R,3R-Fpg)n OMe or Boc(S-Ala-β-2S,3S-Fpg)n OMe were prepared from both enantiomers of syn H-2-(2-F-Phe)-h-PheGly-OH (named β-Fpg) and S-alanine. Our peptides show two appealing features for biomedical applications: the presence of fluorine, attractive for non-covalent interactions, and aryl groups, crucial for π-stacking. A conformational study was performed, using IR, NMR and computational studies of diastereoisomeric tetra- and hexapeptides containing the β2,3-amino acid in the R,R- and S,S-stereochemistry, respectively. We found that the stability of peptide conformation is dependent on the stereochemistry of the β-amino acid. Combining S-Ala with β-2R,3R-Fpg, a stable extended β-strand conformation was obtained. Furthermore, β-2R,3R-Fpg containing hexapeptide self-assembles to form antiparallel β-sheet structure stabilized by intermolecular H-bonds and π,π-interactions. These features make peptides containing the β2,3-fluoro amino acid very appealing for the development of bioactive proteolytically stable foldameric β-sheets as modulators of protein-protein interaction (PPI).

Fluoro-Aryl Substituted α,β2,3-Peptides in the Development of Foldameric Antiparallel β-Sheets: A Conformational Study / R. Bucci, A. Contini, F. Clerici, E.M. Beccalli, Fernandoformaggio, I. Maffucci, S. Pellegrino, M.L. Gelmi. - In: FRONTIERS IN CHEMISTRY. - ISSN 2296-2646. - 7(2019 Apr 02).

Fluoro-Aryl Substituted α,β2,3-Peptides in the Development of Foldameric Antiparallel β-Sheets: A Conformational Study

R. Bucci
Primo
;
A. Contini
Secondo
;
F. Clerici;E.M. Beccalli;I. Maffucci;S. Pellegrino
Penultimo
;
M.L. Gelmi
Ultimo
2019

Abstract

α,β2,3 -Disteroisomeric foldamers of general formula Boc(S-Ala-β-2R,3R-Fpg)n OMe or Boc(S-Ala-β-2S,3S-Fpg)n OMe were prepared from both enantiomers of syn H-2-(2-F-Phe)-h-PheGly-OH (named β-Fpg) and S-alanine. Our peptides show two appealing features for biomedical applications: the presence of fluorine, attractive for non-covalent interactions, and aryl groups, crucial for π-stacking. A conformational study was performed, using IR, NMR and computational studies of diastereoisomeric tetra- and hexapeptides containing the β2,3-amino acid in the R,R- and S,S-stereochemistry, respectively. We found that the stability of peptide conformation is dependent on the stereochemistry of the β-amino acid. Combining S-Ala with β-2R,3R-Fpg, a stable extended β-strand conformation was obtained. Furthermore, β-2R,3R-Fpg containing hexapeptide self-assembles to form antiparallel β-sheet structure stabilized by intermolecular H-bonds and π,π-interactions. These features make peptides containing the β2,3-fluoro amino acid very appealing for the development of bioactive proteolytically stable foldameric β-sheets as modulators of protein-protein interaction (PPI).
English
β2,3-diaryl-amino acid, α, β2,3-peptide, extended peptide, antiparallel β-sheet, conformational analyses, foldamers
Settore CHIM/06 - Chimica Organica
Articolo
Esperti non anonimi
Ricerca di base
Pubblicazione scientifica
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2-apr-2019
Frontiers Media
7
192
11
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Periodico con rilevanza internazionale
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info:eu-repo/semantics/article
Fluoro-Aryl Substituted α,β2,3-Peptides in the Development of Foldameric Antiparallel β-Sheets: A Conformational Study / R. Bucci, A. Contini, F. Clerici, E.M. Beccalli, Fernandoformaggio, I. Maffucci, S. Pellegrino, M.L. Gelmi. - In: FRONTIERS IN CHEMISTRY. - ISSN 2296-2646. - 7(2019 Apr 02).
open
Prodotti della ricerca::01 - Articolo su periodico
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262
Article (author)
si
R. Bucci, A. Contini, F. Clerici, E.M. Beccalli, Fernandoformaggio, I. Maffucci, S. Pellegrino, M.L. Gelmi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/636751
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