Structural mimicry of peptides has witnessed perceptible progress in the last three decades. Reverse turn and β-hairpin units are the smallest secondary structural motifs that are some of the most scrutinized functional cores of peptides and proteins. The practice of mimicking, without altering the function of the bioactive core, ranges from conformational locking of the basic skeleton to total replacement of structural architecture using synthetic analogues. Development of heterogeneous backbones--using unnatural residues in place of natural ones--has broadened further opportunities for efficient structural rigidification. This feature article endeavours to trail the path of progress achieved hitherto and envisage the possibilities that lie ahead in the development of synthetic turn mimetics and hairpin nucleators.

Molecular self-assembly of nonamphiphilic α,β-hybrid foldamers based on urea-tethered anthranilic acid-proline (Ant-Pro) foldamers is reported. These self-assembled hollow vesicular architectures can take up and release the anticancer hydrophobic drug curcumin.

This article details the characteristic conformational features of the Ant‐Pro reverse turn ― a folded pseudo β‐turn motif that displays a closed nine‐membered‐ring hydrogen‐bonded network involving just two amino acid residues, namely anthranilic acid (Ant; a constrained β‐amino acid), and proline (Pro; a constrained α‐amino acid). The results from the extensive investigation of ten crystal structures and their NMR conformations in the solution state provide a clear idea about the conformational characteristics of the Ant‐Pro reverse turn. The Ant and Pro residues, which form the turn segment, maintain a perfect antiperiplanar orientation throughout, leaving little possibility for the formation of the otherwise possible six‐membered hydrogen‐bonding that requires a coplanar disposition of the two amino acid residues, as clearly evident from investigation of several crystal structures. The closed hydrogen‐bonded network observed in the Ant‐Pro reverse turn motif, formed in the forward direction of the sequence (1→2 amino acid interactions) involving only two amino acid residues, is in stark contrast to the native β‐turns that involve four residues to form hydrogen‐bonded network featuring backward 1←4 amino acid interactions. The readily available two‐residue Ant‐Pro motif raises the possibility of a practical utility, particularly in the application of rigidifying flexible peptide backbones by inserting the robust Ant‐Pro reverse turn motifs into their backbone.

This article demonstrates the consequences of incorporating a constrained β-amino acid into a peptide chain and its effect on conformation of oligomers.