抗菌肽及类抗菌肽的设计、合成及应用

Design,Synthesis and Applications of Antimicrobial Peptides and Antimicrobial Peptide-Mimetic Copolymers

抗菌肽是大多数生物体中均存在的阳离子型短肽,其构成了生物免疫系统的重要部分。抗菌肽具有广谱高效的抗菌性和细胞选择性,其独特的膜破坏杀菌机制不易引起病原体的耐药性突变,有望成为新一代控制病原体的有效"抗生素"。但天然抗菌肽的提取成本高、产率低且周期长,不利于大规模生产推广,所以依托化学合成方法合成抗菌肽及其模拟聚合物应运而生。该方法为抗菌肽的设计及合成提供无限可能。本文介绍了抗菌肽的来源、结构和其作用机理并对现有的抗菌肽合成方法进行综述,阐述了现今抗菌肽及类抗菌肽的研究进展以及抗菌肽组装体的应用,最后对抗菌肽及类抗菌肽的发展前景作了展望,为开发高效、低毒的"新一代"抗生素提供重要信息和策略。

Antibiotics resistance of bacteria has caused serious threats to public health and it is urgent to develop novel antibacterial agents that do not induce drug-resistance. Antimicrobial peptides（ AMPs）, constituting important parts of the immune system,are cationic short peptides produced by most living creatures such as bacteria,plants,fish,insects,mammal animals and so on. AMPs possess many excellent properties,including broad-spectrum antibacterial efficacy,high selectivity and unique membrane-destruction bactericidal mechanism.Thus,AMPs have become a promising candidate to overcome superbugs. However,over-costing and timeconsuming production of natural AMPs limit their large-scale application. Therefore,low-cost and convenient synthesis methods have emerged,such as liquid-phase synthesis,solid-phase synthesis and N-carboxyanhydrides（ NCA） ring-opening polymerization. Meanwhile, novel peptide-mimetic antibacterial polymers provide unlimited possibilities for development of peptide-based antibacterial agents and broaden their application fields.In this review,the sources,structure and antibacterial mechanism of AMPs are introduced. The synthesis methods to date of AMPs are also reviewed. Moreover,the development of antimicrobial peptide-mimetic copolymers and application of their assemblies are summarized as well. Finally,the shortcomings and the further development of antimicrobial peptides are discussed,providing advice for development of efficient,low toxicity＂new generation antibiotic＂in the future.