<i>Supporting data for “</i>Harnessing Chemical Proteomics to Uncover Readers of Novel Histone PTMs &Development of YEATS2-targeted Inhibitors and Degraders for Epigenetic Therapies<i>”</i>

In this thesis, we tried to use chemcial proteomics method to uncover the reader proteins of novel histone post translational modifications. At first, we performed experiment to find some potential protein, thus we generated MS data search (As shown in H4K12ac and H4K12acme), in this data, we could select some candidate for our following experiment. Also, we further validated this result by western blot (As shown in WB summary). Also, since the reader proteins serve as attractive drug target, we also tried to develop PROTACs targeting the reader proteins. Through the rational design, we obtained several compounds for the following experiment, to test the efficiency of our candidates, we validated its degradation efficiency through western blot again (As shown in WB summary). In the WB summary, it showed different degradation effect of our product, through this data analysis, we can concluded that most of product did not show high potency, which might require further optimization.本研究采用化学蛋白质组学（chemical proteomics）方法，旨在鉴定新型组蛋白翻译后修饰（histone post-translational modifications）的组蛋白阅读器蛋白（reader proteins）。首先，我们通过实验筛选潜在靶点蛋白，由此生成质谱（mass spectrometry, MS）数据检索结果（详见H4K12ac与H4K12acme部分），并可从中筛选出若干候选蛋白用于后续实验。此外，我们通过蛋白质免疫印迹（Western Blot, WB）对该结果进行了验证（详见WB汇总图）。鉴于组蛋白阅读器蛋白是极具潜力的药物靶点，我们还尝试开发靶向该类蛋白的蛋白降解靶向嵌合体（Proteolysis-Targeting Chimeras, PROTACs）。通过合理设计，我们获得了若干用于后续实验的化合物；为验证候选PROTAC的降解效率，我们再次通过蛋白质免疫印迹进行了验证（详见WB汇总图）。在WB汇总图中可观察到各化合物的降解效果存在差异；通过对该数据的分析，我们得出结论：多数化合物未表现出较高的活性，仍需进一步优化。