AApeptides as a new class of antimicrobial agents

• Published in: Organic & biomolecular chemistry 2013-07, Vol.11 (26), p.4283-429
• Main Authors: Niu, Youhong, Wu, Haifan, Li, Yaqiong, Hu, Yaogang, Padhee, Shruti, Li, Qi, Cao, Chuanhai, Cai, Jianfeng
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - pharmacology; Bacteria - drug effects; Bacterial Infections - drug therapy; Humans; Molecular Sequence Data; Peptidomimetics - chemistry; Peptidomimetics - pharmacology
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c3ob40444g

Antibiotic resistance is an increasing public health concern around the world, and is recognized as one of the greatest threats facing humankind in the 21 st century. Natural antimicrobial peptides (AMPs) are small cationic amphiphilic peptides found in virtually all living organisms, and play a key role in the defense against bacterial infections. Compared with conventional antibiotics, which target specific metabolic processes, AMPs are able to adopt globally amphipathic conformations, and kill bacteria through disruption of their membranes. As such, AMPs do not readily induce drug-resistance. However, AMPs are associated with intrinsic drawbacks such as low-to-moderate activity, susceptibility to enzymatic degradation, and inconvenience for optimization. Recently, we have developed a new class of peptidomimetics termed AApeptides. Such peptide mimics are highly resistant to protease degradation and are straightforward for chemical diversification and development. Our current studies show that AApeptides with globally amphipathic structures can mimic the bactericidal mechanism of AMPs, and display potent and broad-spectrum activity against both Gram-positive and -negative multi-drug-resistant bacteria. In this review, we summarize our current findings of antimicrobial AApeptides, and discuss potential future directions on the development of more potent and specific analogues. Herein we describe the development of AApeptides as a new class of peptidomimetics that mimic natural antimicrobial peptides.