Belharra Therapeutics, San Diego, CA, USA.
Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
Trends Pharmacol Sci. 2024 Nov;45(11):969-981. doi: 10.1016/j.tips.2024.09.001. Epub 2024 Oct 14.
The impact of small molecules in human biology are manifold; not only are they critical regulators of physiological processes, but they also serve as probes to investigate biological pathways and leads for therapeutic development. Identifying the protein targets of small molecules, and where they bind, is critical to understanding their functional consequences and potential for pharmacological use. Over the past two decades, chemical proteomics has emerged as a go-to strategy for the comprehensive mapping of small molecule-protein interactions. Recent advancements in this field, particularly innovations of photoaffinity labeling (PAL)-based methods, have enabled the robust identification of small molecule binding sites on protein targets, often in live cells. In this opinion article, we examine these advancements as well as reflect on how their strategic integration with other emerging tools can advance therapeutic development.
小分子对人类生物学的影响是多方面的；它们不仅是生理过程的关键调节剂，而且还可以作为研究生物途径和治疗开发的探针。确定小分子的蛋白质靶标及其结合位置对于了解其功能后果和药理学用途至关重要。在过去的二十年中，化学蛋白质组学已成为全面绘制小分子-蛋白质相互作用图谱的首选策略。该领域的最新进展，特别是光亲和标记 (PAL) 方法的创新，使人们能够在活细胞中稳健地鉴定蛋白质靶标上的小分子结合位点。在这篇观点文章中，我们检查了这些进展，并反思了它们如何与其他新兴工具进行战略整合以推进治疗开发。
