人工合成型抗菌肽及其药学应用研究进展

Research Advances in the Design of Synthetic Antimicrobial Peptides with Enhanced Therapeutic Potentials

天然抗菌肽(antimicrobial peptides,AMPs)是一类小分子阳离子多肽,具备多种杀菌机制,呈现出高效、广谱的杀菌特性,在抑制耐药性细菌、制备新型抗菌素等方面具有重要的研究价值。以天然抗菌肽为蓝本,设计和开发的人工合成型抗菌肽可以有效克服天然抗菌肽对蛋白酶敏感、细胞毒性较大、生产成本高等缺陷,作为抗感染的潜在药物具有更广阔的应用前景。综述了目前主要的抗菌肽人工改造技术,包括化学修饰法、蛋白质工程技术、计算机分子模拟技术和从头设计最小化抗菌肽方法的研究进展,并对人工合成抗菌肽作为抗菌药物的应用现状进行了简介。

Natural antimicrobial peptides （AMPs） are small cationic peptides with potent and broad- spectrum antimierobial activities which have received great attention as a promising antibiotic candidates to overcome the global epidemic of antibiotics-resistant infections. Natural AMPs has provided a wealth of information on the structure-activity relationship accounting for antimicrobial activity to design novel synthetic AMPs with improved protease-resistance, reduced cost of production and less hemolysis and toxicity, which greatly promotes the potential of synthetic peptides as anti-infectious agent. Firstly the general strategies and technologies employed in the design and optimization of synthetic peptides, i.e. , chemical modification, protein engineering, in silieo design and screening, and minimalist de novo design were summarized. Finally, the synthetic AMPs in clinical trail with outstanding therapeutic potentials and future perspectives of improved AMPs for therapeutic applications were highlighted.