摘要
当前抗菌药物面临日趋严重的抗生素耐药性问题,亟需新结构或新作用机制的抗菌药。抗菌肽因其具有广谱抗菌活性和独特的杀菌机制,被认为是对抗多重耐药细菌的潜在治疗药物,有很好的发展前景。但是,抗菌肽存在结构不稳定,易被蛋白酶水解等缺点,为抗菌肽的临床转化带来了阻碍。提高多肽结构稳定性可以使用非天然氨基酸修饰、环化等方法,近年来一种被称为订书修饰的特殊环化方法受到广泛关注,包括使用全碳氢链、三唑基或者硫代碳链桥环钉子等。订书结构的引入可以提高抗菌肽结构的稳定性,尤其是α-螺旋结构的稳定性,增强抗菌肽的活性,还可以抵抗蛋白酶水解,但也存在提高溶血毒副作用的可能。本文介绍了订书肽的结构、合成以及研究中的订书抗菌肽,并讨论了影响其活性的主要因素,以期为新型抗耐药菌药物研发提供帮助。
Current antimicrobial chemotherapy faces a significant threat from antibiotic resistance,and novel antimicrobial medication architectures or modes of action are desperately needed.Antimicrobial peptides,due to their broad-spectrum antimicrobial activity and unique bactericidal mechanisms,are considered potential therapeutic agents against multidrug-resistant bacteria with good development prospects.However,antimicrobial peptides have disadvantages such as structural instability and susceptibility to proteolytic degradation,which hinder the clinical translation of these peptides.Improving the structural stability of peptides can be achieved by various methods,such as non-natural amino acid modifications and cyclization.In recent years,a particular cyclization method called stapling modification has gained significant attention.This method involves the use of all carbon-hydrogen,triazole or thioether based staples.The addition of stapling structures can enhance antimicrobial activity,improve the stability of antimicrobial peptide structures,especiallyα-helical structures,and resist proteolytic degradation.However,it may also increase hemolytic side effects.This review introduces the structure,and synthesis of stapled peptides.In an effort to support the creation of novel antimicrobial medications against resistant bacteria,we present instances of stapled antimicrobial peptides in research and go over the key variables affecting their efficacy..
作者
莫沁梓
郑珩
Mo Qin-zi;Zheng Heng(School of Basic Medical Sciences,Guangxi Medical University,Nanning 530199;College of Life Science and Technology,China Pharmaceutical University,Nanjing 210009)
出处
《国外医药（抗生素分册）》
CAS
2024年第4期217-225,共9页
World Notes on Antibiotics
基金
国家自然科学基金(项目编号82070767)。
关键词
抗菌肽
订书肽
环化修饰
稳定性
结构
antimicrobial peptides
stapled peptides
cyclization modifications
stability
structure
作者简介
莫沁梓,在读本科生,主要从事临床医学研究;通信作者:郑珩,副教授,主要从事微生物与生化药学研究工作。
