ABSTRACT In this study, the efficient design and synthesis of a novel peptide bioisosteres for selective folding into a hairpin‐like structure has been reported. The peptide mimetic comprises β‐alanine, L‐leucine, α‐amino isobutyric acid, m ‐nitro cinnamic acid has been synthesized via solution‐phase coupling methods. A hairpin conformation and extended β‐pleated parallel sheet assembly have been characterized in solution as well as in solid state. The key to this success was the use of β‐alanine as a flexible amino acid that can accommodate a wide range of dihedral angles proximal to the binol core. In its solid state, the molecule adopts a hairpin conformation with two perpendicular naphthalene rings. The centrally located binol segment act as bioisosteres and nucleates a chain reversal in the hairpin conformation. Two intramolecular cross‐strand hydrogen bonds stabilize the hairpin. Moreover, the intermolecular NH…O═C hydrogen bonds connect the hairpins into an infinitely extended parallel β‐sheet. The structure is also stabilized by face to edge π‐stacking interactions. This peptide bioisosteres represents a promising tool for foldamer design.
Shit et al. (Thu,) studied this question.