Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

IF 2.2 4区 化学 Q2 CHEMISTRY, ORGANIC
Andreas Wiest, Pavel Kielkowski
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引用次数: 0

Abstract

Identification of interactions between proteins and natural products or similar active small molecules is crucial for understanding of their mechanism of action on a molecular level. To search elusive, often labile, and low-abundant conjugates between proteins and active compounds, chemical proteomics introduces a feasible strategy that allows to enrich and detect these conjugates. Recent advances in mass spectrometry techniques and search algorithms provide unprecedented depth of proteome coverage and the possibility to detect desired modified peptides with high sensitivity. The chemical ‘linker’ connecting an active compound–protein conjugate with a detection tag is the critical component of all chemical proteomic workflows. In this review, we discuss the properties and applications of different chemical proteomics linkers with special focus on their fragmentation releasing diagnostic ions and how these may improve the confidence in identified active compound–peptide conjugates. The application of advanced search options improves the identification rates and may help to identify otherwise difficult to find interactions between active compounds and proteins, which may result from unperturbed conditions, and thus are of high physiological relevance.

Abstract Image

Beilstein J. Org. Chem. 2024, 20, 2323–2341. doi:10.3762/bjoc.20.199

利用化学蛋白质组学连接体的诊断离子改进天然产品蛋白质靶标的解卷积分析
摘要确定蛋白质与天然产物或类似活性小分子之间的相互作用对于在分子水平上了解它们的作用机制至关重要。为了寻找蛋白质与活性化合物之间难以捉摸、通常易变和低丰度的共轭物,化学蛋白质组学引入了一种可行的策略,可以富集和检测这些共轭物。质谱技术和搜索算法的最新进展为蛋白质组的覆盖提供了前所未有的深度,并为高灵敏度地检测所需的修饰肽提供了可能性。连接活性化合物–蛋白质共轭物和检测标签的化学连接物是所有化学蛋白质组工作流程的关键组成部分。在这篇综述中,我们将讨论不同化学蛋白质组学连接物的特性和应用,特别关注它们释放诊断离子的碎片,以及这些连接物如何提高已鉴定活性化合物–肽共轭物的可信度。高级搜索选项的应用提高了鉴定率,并有助于鉴定活性化合物与蛋白质之间原本难以发现的相互作用,这种相互作用可能是在未受干扰的条件下产生的,因此具有很高的生理相关性。Chem.2024, 20, 2323–2341. doi:10.3762/bjoc.20.199
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来源期刊
CiteScore
4.90
自引率
3.70%
发文量
167
审稿时长
1.4 months
期刊介绍: The Beilstein Journal of Organic Chemistry is an international, peer-reviewed, Open Access journal. It provides a unique platform for rapid publication without any charges (free for author and reader) – Platinum Open Access. The content is freely accessible 365 days a year to any user worldwide. Articles are available online immediately upon publication and are publicly archived in all major repositories. In addition, it provides a platform for publishing thematic issues (theme-based collections of articles) on topical issues in organic chemistry. The journal publishes high quality research and reviews in all areas of organic chemistry, including organic synthesis, organic reactions, natural product chemistry, structural investigations, supramolecular chemistry and chemical biology.
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