Stabilization of two smallest possible diastereomeric β-hairpins in a water soluble tetrapeptide containing non-coded α-amino isobutyric acid (Aib) and m-amino benzoic acid

Single crystal X-ray diffraction study reveals that the water soluble tetrapeptide H2N–Ile–Aib–Leu–m-ABA–CO2H, containing non-coded Aib (α-amino isobutyric acid) and m-ABA (meta  -amino benzoic acid), crystallizes with two smallest possible diastereomeric β-hairpin molecules in the asymmetric unit. Although in both of the molecules the chiralities at Ile(1) and Leu(3) are S, a conformational reversal in the back bone chain is observed to produce the β-hairpins with β-turn conformations of type II and II′. Interestingly Aib which is known to adopt helical conformation, adopts unusual semi-extended conformation with ϕϕ: −49.5(5)°, ψ  : 135.2(5)° in type II and ϕϕ: 50.6(6)°, ψ: −137.0(4)° in type II′ for occupying the i + 1 position of the β-turns. The two hairpin molecules are further interlocked through intermolecular hydrogen bonds and electrostatic interactions between –CO2- and −+NH3 groups to form dimeric supramolecular β-hairpin aggregate in the crystal state. The CD measurement and 2D NMR study of the peptide in aqueous medium support the existence of β-hairpin structure in water.