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Mechanistic Landscape of Membrane-Permeabilizing Peptides.
Chemical Reviews ( IF 51.4 ) Pub Date : 2019-01-09 , DOI: 10.1021/acs.chemrev.8b00520 Shantanu Guha 1 , Jenisha Ghimire 1 , Eric Wu 1 , William C Wimley 1
Chemical Reviews ( IF 51.4 ) Pub Date : 2019-01-09 , DOI: 10.1021/acs.chemrev.8b00520 Shantanu Guha 1 , Jenisha Ghimire 1 , Eric Wu 1 , William C Wimley 1
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Membrane permeabilizing peptides (MPPs) are as ubiquitous as the lipid bilayer membranes they act upon. Produced by all forms of life, most membrane permeabilizing peptides are used offensively or defensively against the membranes of other organisms. Just as nature has found many uses for them, translational scientists have worked for decades to design or optimize membrane permeabilizing peptides for applications in the laboratory and in the clinic ranging from antibacterial and antiviral therapy and prophylaxis to anticancer therapeutics and drug delivery. Here, we review the field of membrane permeabilizing peptides. We discuss the diversity of their sources and structures, the systems and methods used to measure their activities, and the behaviors that are observed. We discuss the fact that "mechanism" is not a discrete or a static entity for an MPP but rather the result of a heterogeneous and dynamic ensemble of structural states that vary in response to many different experimental conditions. This has led to an almost complete lack of discrete three-dimensional active structures among the thousands of known MPPs and a lack of useful or predictive sequence-structure-function relationship rules. Ultimately, we discuss how it may be more useful to think of membrane permeabilizing peptides mechanisms as broad regions of a mechanistic landscape rather than discrete molecular processes.
中文翻译：
膜透化肽的机制景观。
膜透化肽 (MPP) 与其作用的脂质双层膜一样普遍存在。大多数膜透化肽由所有生命形式产生，用于进攻或防御其他生物体的膜。正如大自然发现了它们的许多用途一样，转化科学家几十年来一直致力于设计或优化膜透化肽，用于实验室和临床应用，范围从抗菌和抗病毒治疗和预防到抗癌治疗和药物输送。在这里，我们回顾一下膜透化肽领域。我们讨论其来源和结构的多样性、用于衡量其活动的系统和方法以及观察到的行为。我们讨论这样一个事实：“机制”对于 MPP 来说不是一个离散或静态实体，而是结构状态的异质和动态集合的结果，这些状态响应许多不同的实验条件而变化。这导致在数千个已知的MPP中几乎完全缺乏离散的三维活性结构，并且缺乏有用的或可预测的序列-结构-功能关系规则。最后，我们讨论了将膜透化肽机制视为机械景观的广泛区域而不是离散的分子过程可能更有用。
更新日期：2019-01-09
中文翻译：
膜透化肽的机制景观。
膜透化肽 (MPP) 与其作用的脂质双层膜一样普遍存在。大多数膜透化肽由所有生命形式产生，用于进攻或防御其他生物体的膜。正如大自然发现了它们的许多用途一样，转化科学家几十年来一直致力于设计或优化膜透化肽，用于实验室和临床应用，范围从抗菌和抗病毒治疗和预防到抗癌治疗和药物输送。在这里，我们回顾一下膜透化肽领域。我们讨论其来源和结构的多样性、用于衡量其活动的系统和方法以及观察到的行为。我们讨论这样一个事实：“机制”对于 MPP 来说不是一个离散或静态实体，而是结构状态的异质和动态集合的结果，这些状态响应许多不同的实验条件而变化。这导致在数千个已知的MPP中几乎完全缺乏离散的三维活性结构，并且缺乏有用的或可预测的序列-结构-功能关系规则。最后，我们讨论了将膜透化肽机制视为机械景观的广泛区域而不是离散的分子过程可能更有用。
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