Chemical modifications to increase the therapeutic potential of antimicrobial peptides
Chemical modifications to increase the therapeutic potential of antimicrobial peptides
复制标题
化学修饰可提高抗菌肽的治疗潜力
DOI：
10.1016/j.peptides.2021.170666
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发表时间：
2021-10-07
期刊：
影响因子：
3
通讯作者：
Zhang, Zhiye
中科院分区：
文献类型：
--
作者：
Han, Yajun;Zhang, Manli;Zhang, Zhiye
抗生素的持续使用伴随着抗药性细菌菌株的迅速出现和传播。抗菌肽（Antimicrobial peptides，AMP），又称宿主防御肽（host defense peptides），是一种理想的抗菌剂，具有抗菌活性强、抗菌速度快、抗菌谱广、耐药性低、抗生物膜活性强、对代谢不活跃的微生物具有致死性等特点。然而，几个关键的缺点限制了AMP作为临床药物的使用，例如，在体内易受影响，全身使用时具有毒性，并且生产成本高。基于近年来的研究成果和我们自己的经验，本文总结了抗菌肽的化学修饰和关键设计策略，包括1）增强抗菌活性，2）提高体内有效性，3）降低毒性，这可能有助于抗菌肽的设计和优化，用于候选药物的开发。我们还讨论了目前的挑战，在优化的AMP和未来的关注的耐药性和交叉耐药性的AMP作为治疗药物的发展。
The continued use of antibiotics has been accompanied by the rapid emergence and spread of antibiotic-resistant strains of bacteria. Antimicrobial peptides (AMPs), also known as host defense peptides, show multiple features as an ideal antimicrobial agent, including potent, rapid, and broad-spectrum antimicrobial activity, low promotion of antimicrobial resistance, potent anti-biofilm activity, and lethality against metabolically inactive microorganisms. However, several crucial drawbacks constrain the use of AMPs as clinical drugs, e.g., liability in vivo, toxicity when used systemically, and high production costs. Based on recent findings and our own experiences, here we summarize some chemical modifications and key design strategies to increase the therapeutic potential of AMPs, including 1) enhancing antimicrobial activities, 2) improving in vivo effectiveness, and 3) reduction in toxicity, which may facilitate the design and optimization of AMPs for the development of drug candidates. We also discuss the present challenges in the optimization of AMPs and future concerns about the resistance and cross-resistance to AMPs in the development of AMPs as therapeutic drugs.