Fluoro-Aryl Substituted alpha,beta(2,3)-Peptides in the Development of Foldameric Antiparallel beta-Sheets: A Conformational Study

Bucci, Raffaella; Contini, Alessandro; Clerici, Francesca; Beccalli, Egle Maria; Formaggio, Fernando; Maffucci, Irene; Pellegrino, Sara; Gelmi, Maria Luisa ✉

English Scientific Article (Journal Article)
Published: FRONTIERS IN CHEMISTRY 2296-2646 7 Paper: 192 , 11 p. 2019
  • SJR Scopus - Chemistry (miscellaneous): Q1
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Subjects:
    alpha,beta(2,3)-Disteroisomeric foldamers of general formula Boc(S-Ala-beta-2R,3R-Fpg)(n) OMe or Boc(S-Ala-beta-2S,3S-Fpg)(n) OMe were prepared from both enantiomers of syn H-2-(2-F-Phe)-h-PheGly-OH (named beta-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 pi-stacking. A conformational study was performed, using IR, NMR and computational studies of diastereoisomeric tetra- and hexapeptides containing the beta(2,3)-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 beta-amino acid. Combining S-Ala with beta-2R,3R-Fpg, a stable extended beta-strand conformation was obtained. Furthermore, beta-2R,3R-Fpg containing hexapeptide self-assembles to formantiparallel beta sheet structure stabilized by intermolecular H-bonds and pi, pi-interactions. These features make peptides containing the beta(2,3)-fluoro amino acid very appealing for the development of bioactive proteolytically stable foldameric beta-sheets as modulators of protein-protein interaction (PPI).
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    2020-08-15 13:08