Title:γ-AApeptides as a New Class of Peptidomimetics: Design, Synthesis, and Applications
Volume: 21
Issue: 28
Author(s): Ma Su, Yifan Zhu, Wei Wang*, Feng Liu*Huanqiu Li *
Affiliation:
- Department of Neurology, Hebei Yanda Hospital, Sanhe, Hebei,China
- Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123,China
- Department of Medicinal Chemistry, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123,China
Keywords:
Peptidomimetics, γ-AApeptides, AMPs, Combinatorial screening, Rational design, Synthesis, Applications.
Abstract:
Peptidomimetics are studied for medicinal application because of their 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 carried out 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 selfassembly
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. Anticancer
agents, anti-T2DM (Type 2 diabetes mellitus) agents, anti-HIV (human immuno-deficiency
virus) agents and anti-Alzheimer’s disease agents were developed by combinatorial screening and
rational design. Furthermore, γ-AApeptides as biopolymers, nanomaterials, supramolecular structures
and self-assembly architectures were studied due to their unique backbone structures. Therefore,
γ-AApeptides may play an important role in the development of peptidomimetics.
