Enforcing Periodic Secondary Structures in Hybrid Peptides: A Novel Hybrid Foldamer Containing Periodic γ-Turn Motifs

This note describes the design, synthesis, and conformational
studies of a novel hybrid foldamer that adopts a definite
compact, three-dimensional structure determined by a combined effect of the special conformational properties of the
foldamer constituents. The striking feature of this de novo
designed foldamer is its ability to display periodic γ-turn
conformations stabilized by intramolecular hydrogen bonds.
Conformational investigations by single-crystal X-ray studies,
solution-state NMR, and ab initio MO theory at the HF/6-31G* level strongly support the prevalence of γ-turn motifs
in both the di- and tetrapeptide foldamers, which are
presumably stabilized by bifurcated hydrogen bonds in the
solid and solution states. The strategy disclosed herein for
the construction of hybrid foldamers with periodic γ-turn
motifs has the potential to significantly augment the conformational space available for foldamer design with diverse
backbone structures and conformations.