γ-AApeptides as a New Class of Peptidomimetics

Abstract

Sequence-specific peptidomimetics are molecules that mimic the structure and function of peptides and proteins. With new backbones and molecular frameworks, peptidomimetics are of considerable interest in addressing challenges encountered in chemical biology and biomedical sciences. Based on the γ-PNA backbone, a new class of peptidomimetics - "γ-AApeptides" were recently developed. Both linear and cyclic γ-AApeptides can be synthesized with high efficiency. Compared with α-peptides, γ-AApeptides are resistant to enzymatic degradation, and amendable to diversification with a variety of chemical groups. Moreover, they could mimic primary and secondary structure, as well as the function of peptides, and show promise in biological applications, such as the development of new agents combating bacteria, cancer, and Alzheimer's disease. A few research outcomes of γ-AApeptides are highlighted in this Concept article, and a future perspective is also proposed.

Keywords: anti-Aβ aggregation; antimicrobial; combinatorial chemistry; folding; peptides; peptidomimetics.