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基于活性的探针在致病菌中的应用:药物靶点和分子特异性研究。

Activity-based probes in pathogenic bacteria: Investigating drug targets and molecule specificity.

机构信息

Department of Chemistry, University of Minnesota, Minneapolis, MN, United States.

Department of Chemistry, University of Minnesota, Minneapolis, MN, United States; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, United States; Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, United States; Department of Pharmacology, University of Minnesota, Minneapolis, MN, United States.

出版信息

Curr Opin Chem Biol. 2023 Oct;76:102359. doi: 10.1016/j.cbpa.2023.102359. Epub 2023 Jul 3.

Abstract

Bacteria comprise complex communities within our bodies and largely have beneficial roles, however a small percentage are pathogenic. While all pathogens are important to public health, immediate action is necessary to combat bacterial strains developing pan- and multi-resistance to antibiotics. As present therapeutics fail to tackle this problem, novel strategies are required to address this threat. Activity-based probes (ABPs) are one method to investigate proteins of interest in pathogens. These probes can serve multiple purposes to better our understanding of bacterial pathogenicity. Herein, we highlight recent studies that used ABPs to identify new drug targets or visualize antibiotic resistance- or bacterial virulence-associated proteins, and introduce strategies to determine the specificity of ABPs within a targeted enzyme class.

摘要

细菌在我们体内构成了复杂的群落,它们在很大程度上具有有益的作用,但一小部分是病原性的。虽然所有的病原体都对公共健康很重要,但必须立即采取行动,以防止细菌对抗生素产生泛耐药和多重耐药。由于目前的治疗方法无法解决这个问题,因此需要新的策略来应对这一威胁。活性探针(ABP)是一种研究病原体中感兴趣蛋白质的方法。这些探针可以有多种用途,以帮助我们更好地了解细菌的致病性。本文重点介绍了最近使用 ABP 来鉴定新的药物靶点或可视化抗生素耐药性或细菌毒力相关蛋白的研究,并介绍了在靶向酶类中确定 ABP 特异性的策略。

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本文引用的文献

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Molecular mechanisms of antibiotic resistance revisited.抗生素耐药性的分子机制再探讨。
Nat Rev Microbiol. 2023 May;21(5):280-295. doi: 10.1038/s41579-022-00820-y. Epub 2022 Nov 21.
7
Antibiotics in the pipeline: a literature review (2017-2020).正在研发中的抗生素:文献综述(2017-2020 年)。
Infection. 2022 Jun;50(3):553-564. doi: 10.1007/s15010-021-01709-3. Epub 2021 Oct 4.

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