Target engagement in bacterial and protozoan pathogens: in vitro and cellular assays for drug discovery

IF 7.8 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology Pub Date : 2026-02-01 Epub Date: 2025-11-28 DOI:10.1016/j.sbi.2025.103194

Priscila Z. Ramos , Carolina M.C. Catta-Preta , Rafael M. Couñago

引用次数: 0

Abstract

Target engagement (TE) assays are essential for confirming on-target activity, guiding medicinal chemistry, and linking molecular interactions to phenotypic outcomes. Despite their success in human drug discovery, their application to bacterial and protozoan pathogens remains limited due to biological complexity, technical barriers, and lack of high-quality chemical tools and protein reagents. This review surveys current TE strategies and highlights emerging tools such as live-cell bioluminescence resonance energy transfer, cellular thermal shif assay, and chemoproteomics. Expanding TE in pathogen research will deepen mechanistic insights, reduce development risk, and improve the chances of delivering safer, more effective anti-infective therapies.

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细菌和原生动物病原体的靶标参与：药物发现的体外和细胞分析

靶接合（TE）分析对于确认靶上活性、指导药物化学以及将分子相互作用与表型结果联系起来至关重要。尽管它们在人类药物发现方面取得了成功，但由于生物复杂性、技术障碍以及缺乏高质量的化学工具和蛋白质试剂，它们在细菌和原生动物病原体上的应用仍然有限。本文综述了当前的TE策略，并重点介绍了新兴的工具，如活细胞生物发光共振能量转移、细胞热转移测定和化学蛋白质组学。在病原体研究中扩大TE将加深对机制的认识，降低发展风险，并提高提供更安全、更有效的抗感染治疗的机会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current opinion in structural biology 生物-生化与分子生物学

CiteScore

12.20

自引率

2.90%

发文量

179

审稿时长

6-12 weeks

期刊介绍： Current Opinion in Structural Biology (COSB) aims to stimulate scientifically grounded, interdisciplinary, multi-scale debate and exchange of ideas. It contains polished, concise and timely reviews and opinions, with particular emphasis on those articles published in the past two years. In addition to describing recent trends, the authors are encouraged to give their subjective opinion of the topics discussed. In COSB, we help the reader by providing in a systematic manner: 1. The views of experts on current advances in their field in a clear and readable form. 2. Evaluations of the most interesting papers, annotated by experts, from the great wealth of original publications. [...] The subject of Structural Biology is divided into twelve themed sections, each of which is reviewed once a year. Each issue contains two sections, and the amount of space devoted to each section is related to its importance. -Folding and Binding- Nucleic acids and their protein complexes- Macromolecular Machines- Theory and Simulation- Sequences and Topology- New constructs and expression of proteins- Membranes- Engineering and Design- Carbohydrate-protein interactions and glycosylation- Biophysical and molecular biological methods- Multi-protein assemblies in signalling- Catalysis and Regulation