Institute of Bioorganic Chemistry of Russian Academy of Science, Moscow, Russian Federation.
Division of Pulmonary, Critical Care, Sleep Medicine and Physiology, University of California San Diego, La Jolla, CA, USA.
Biochimie. 2023 Nov;214(Pt B):216-227. doi: 10.1016/j.biochi.2023.07.016. Epub 2023 Jul 25.
Antimicrobial peptides (AMPs) are essential for defence against pathogens in all living organisms and possessed activities against bacteria, fungi, viruses, parasites and even cancer cells. AMPs are short peptides containing 12-100 amino acids conferring a net positive charge and an amphiphilic property in most cases. Although, anionic AMPs also exist. AMPs can be classified based on the types of secondary structures, charge, hydrophobicity, amino acid composition, length, etc. Their mechanism of action usually includes a membrane disruption process through pore formation (three different models have been described, barrel-stave, toroidal or carpet model) but AMPs can also penetrate and impair intracellular functions. Besides their activity against pathogens, they have also shown immunomodulatory properties in complex scenarios through many different interactions. The aim of this review to summarize knowledge about AMP's and discuss the potential application of AMPs as therapeutics, the challenges due to their limitations, including their susceptibility to degradation, the potential generation of AMP resistance, cost, etc. We also discuss the current FDA-approved drugs based on AMPs and strategies to circumvent natural AMPs' limitations.
抗菌肽(AMPs)是所有生物体防御病原体所必需的,对细菌、真菌、病毒、寄生虫甚至癌细胞都具有活性。AMPs 是含有 12-100 个氨基酸的短肽,在大多数情况下赋予净正电荷和两亲性。尽管也存在阴离子 AMPs。可以根据二级结构、电荷、疏水性、氨基酸组成、长度等类型对 AMPs 进行分类。它们的作用机制通常包括通过形成孔(已描述了三种不同的模型,桶棒、环或地毯模型)破坏细胞膜的过程,但 AMPs 也可以穿透并损害细胞内功能。除了对病原体的活性外,它们还通过许多不同的相互作用在复杂情况下显示出免疫调节特性。本综述的目的是总结 AMP 的知识,并讨论 AMP 作为治疗剂的潜在应用,以及由于其局限性(包括易降解、潜在 AMP 耐药性的产生、成本等)带来的挑战。我们还讨论了基于 AMP 的当前 FDA 批准药物以及规避天然 AMP 局限性的策略。