抗菌肽的设计原则。
Peptide Design Principles for Antimicrobial Applications.
机构信息
Synthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; The Center for Microbiome Informatics and Therapeutics, Cambridge, MA 02139, USA; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, São Paulo 09210580, Brazil.
Synthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, and Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; The Center for Microbiome Informatics and Therapeutics, Cambridge, MA 02139, USA.
出版信息
J Mol Biol. 2019 Aug 23;431(18):3547-3567. doi: 10.1016/j.jmb.2018.12.015. Epub 2019 Jan 3.
The increased incidence of bacterial resistance to available antibiotics represents a major global health problem and highlights the need for novel anti-infective therapies. Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics. AMPs are versatile, have almost unlimited sequence space, and can be tuned for broad-spectrum or specific activity against microorganisms. However, several obstacles remain to be overcome in order to develop AMPs for medical use, such as toxicity, stability, and bacterial resistance. We lack standard experimental procedures for quantifying AMP activity and do not yet have a clear picture of the mechanisms of action of AMPs. The rational design of AMPs can help solve these issues and enable their use as new antimicrobials. Here we provide an overview of the main physicochemical features that can be engineered to achieve enhanced bioactivity and describe current strategies being used to design AMPs.
现有抗生素的细菌耐药性不断增加，这是一个全球性的主要健康问题，突显了开发新型抗感染疗法的必要性。抗菌肽（antimicrobial peptides，AMPs）是传统抗生素的有前途的替代品。AMPs 具有多功能性，几乎有无穷无尽的序列空间，可以针对微生物进行广谱或特异性活性的调整。然而，为了将 AMP 开发用于医学用途，仍然存在几个需要克服的障碍，例如毒性、稳定性和细菌耐药性。我们缺乏量化 AMP 活性的标准实验程序，也没有清楚地了解 AMP 作用机制。对抗 AMP 的理性设计可以帮助解决这些问题，并使其能够作为新的抗菌药物使用。在这里，我们提供了可以设计以实现增强的生物活性的主要理化特性的概述，并描述了目前用于设计 AMP 的策略。
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