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).
