Conformational and self-assembly studies of helix forming hexapeptides containing two α-amino isobutyric acids

Single crystal X-ray diffraction studies reveal that three hexapeptides with general formula Boc–Ile–Aib–Xx–Ile–Aib–Yy–OMe, where Xx and Yy are Leu in peptide I, Leu and Phe in peptide II, and Phe and Leu in peptide III, respectively, adopt equivalent conformations that can be described as mixed 310/α-helice with two 4→1 and two 5→1 intramolecular N–H⋯Odouble bond; length as m-dashC H-bonds. The peptides do not generate any helix-terminating Schellman motif despite having Aib at the penultimate position from C-terminus. In the crystalline state, the helices are packed in head-to-tail fashion through intermolecular hydrogen bonds to create supramolecular helical structures. The CD studies of the three hexapeptides in acetonitrile indicate that they are folded in well-developed 310-helical structures. NMR studies of peptide I in CDCl3 also suggest the formation of a homogeneous 310-helical structure. The field emission scanning electron microscopic (FE-SEM) images of peptide II in the solid state reveal a non-twisted ribbon-like morphology, which is formed through lateral association of non-twisted filaments.