α,β
2,3
-Disteroisomeric foldamers of general formula Boc(
S-
Ala-β-2
R
,3
R-
Fpg)
n
OMe or Boc(
S-
Ala-β-2
S
,3
S-
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 β
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 β-amino acid. Combining
S
-Ala with β-2
R,3R
-Fpg, a stable extended β-strand conformation was obtained. Furthermore, β-2
R,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 β
2,3
-fluoro amino acid very appealing for the development of bioactive proteolytically stable foldameric β-sheets as modulators of protein-protein interaction (PPI).