γ-AApeptides as a New Strategy for Therapeutic Development

A new class of peptidomimetics termed as "γ-AApeptides" was recently developed by our group. Similar to other peptidomimetics, γ-AApeptides are resistant to proteolytic degradation, and possess limitless potential to introduce chemically diverse functional groups. γ-AApeptides have shown great promise in biomedical applications. In this article, we will review a few examples of γ-AApeptides with biological potential. Certain γ-AApeptides can permeate cell membranes and therefore they can be used as potential drug carrier. γ-AApeptides can also bind to HIV RNA with high specificity and affinity, suggesting their potential application as anti-HIV agents. Moreover, they can mimic host-defense peptides and display potent and broad-spectrum activity towards a range of drug-resistant bacterial pathogens. They are also potential anti-cancer agents. For instance, they have shown great promise in targeted imaging of tumor in mouse model, and they are also capable of disrupting p53/DNA interactions, and thus antagonize STAT3 signaling pathway. Recently, from combinatorial screening, γ-AApeptides are identified to inhibit Aβ peptide aggregation, and thus they can be developed into potential anti- Alzheimer’s disease agent.