Considerations for designing chemical screening strategies in plant biology.

Considerations for designing chemical screening strategies in plant biology.
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DOI:
10.3389/fpls.2015.00131
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发表时间:
2015
影响因子:
5.6
通讯作者:
Meesters C
Meesters C
中科院分区:
生物学2区
文献类型:
--
作者:
Serrano M;Kombrink E;Meesters C

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传统上,生物学家经常使用经典的遗传方法来表征和剖析植物过程。然而,这种策略常常受到基因功能的冗余、致死性或多效性的损害,从而阻碍了可行突变体的分离。化学遗传学方法已被认为是一种替代实验策略,有可能规避这些问题。它依赖于小分子通过与蛋白质靶标特异性结合来改变生物过程的能力,从而有条件地改变蛋白质功能,其表型类似于编码基因的突变。成功的化学筛选活动包括三个同样重要的要素:(1) 可靠、稳健和定量的生物测定,可以区分强效和弱效化合物;(2) 对候选化合物进行严格的验证过程,以确定其选择性;(3) 阐明化合物作用模式和分子靶标的实验策略。在这篇综述中,我们将讨论这一总体策略的细节以及值得考虑的其他方面,以便充分利用化学方法为植物生物学提供的力量。此外,我们将重点介绍最近植物系统化学筛选的一些成功案例,这些案例可以作为实施未来化学生物学项目的教学实例。
Traditionally, biologists regularly used classical genetic approaches to characterize and dissect plant processes. However, this strategy is often impaired by redundancy, lethality or pleiotropy of gene functions, which prevent the isolation of viable mutants. The chemical genetic approach has been recognized as an alternative experimental strategy, which has the potential to circumvent these problems. It relies on the capacity of small molecules to modify biological processes by specific binding to protein target(s), thereby conditionally modifying protein function(s), which phenotypically resemble mutation(s) of the encoding gene(s). A successful chemical screening campaign comprises three equally important elements: (1) a reliable, robust, and quantitative bioassay, which allows to distinguish between potent and less potent compounds, (2) a rigorous validation process for candidate compounds to establish their selectivity, and (3) an experimental strategy for elucidating a compound's mode of action and molecular target. In this review we will discuss details of this general strategy and additional aspects that deserve consideration in order to take full advantage of the power provided by the chemical approach to plant biology. In addition, we will highlight some success stories of recent chemical screenings in plant systems, which may serve as teaching examples for the implementation of future chemical biology projects.
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