γ‑AApeptides as a New Class of Peptidomimetics: Design, Synthesis, and Applications

Curr Top Med Chem. 2021 Jul 27. doi: 10.2174/1568026621666210727160852. Online ahead of print.ABSTRACTPeptidomimetics are studied for medicinal application because of its ability to mimic hierarchical structures of peptides and proteins. To break the limitation and expand the peptidomimetics family, a new class of peptidomimetics based on peptide nucleic acids (PNAs) backbone - "γ-AApeptides" was developed. Compared with previous peptidomimetics, γ-AApeptides possess prominent advantages such as resistance to proteolytic degradation, enhanced chemodiversity, good selectivity and outstanding bioactivity. The synthesis of γ-AApeptides is using a ''monomer building block'' strategy which is facile and efficient. γ-AApeptides are able to mimic primary and secondary structures of therapeutic peptides which make them promising candidates for molecular probes and potential drug leads. In the past decade, several interesting structures and applications of γ-AApeptides have been developed by different approaches such as structure-based design, combinatorial library screening, and peptides self-assembly and folding. By following the mechanism of host-defense peptides (HDPs), antibiotic γ-AApeptides showed broad-spectrum activity. At the same time, γ-AApeptides can be used for combinatorial library screening because of their structural stability and their chemodiversity. Anti-cancer agents, anti-T2DM (Type 2 diabetes mellitus) agents, anti-HIV (human immuno-deficiency virus) agen...
Source: Topics in HIV Medicine - Category: Infectious Diseases Authors: Source Type: research