Ligand-direct Radical Chemistry for Target Labelling in Living Cell

用于活细胞中靶标标记的配体直接自由基化学

• 批准号: 20K15414
• 负责人: 茅 迪
• 金额: $ 2.66万
• 依托单位: University of the Ryukyus
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2020
• 资助国家: 日本
• 起止时间: 2020-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20K15414/
• 关键词: Radical Chemistry; medicinal chemistry; chemical biology; Protein; Small molecule; Target engagement

To achieve the research goal, we firstly selected Carvedilol, a famous drug targeting on beta-receptor, as a model. Although Carvedilol was highly photo sensitive, its reaction with beta-receptor was not observed. Tamoxifen and Carprofen, the other two photo sensitive drugs, were next selected to validate the hypothesis. However, no photo reaction was observed between the drugs and their target proteins. The results suggested that the mechanism of photo-induced degradation of SQS might be unique. We next investigated the types of radicals that generated by YM53601. Highly reactive hydroxyl radical was indentified. The relationship between hydroxyl radical and SQS degradation are now under investigation.

为了实现研究目标，我们首先选择了针对β受体的著名药物卡维地洛作为研究模型。虽然卡维地洛具有高度的光敏性，但未观察到其与β受体的反应。接下来选择了另外两种光敏药物他莫昔芬和卡洛芬来验证这一假设。然而，这些药物和它们的目标蛋白之间没有光反应。结果表明，光诱导降解SQS的机理可能是独特的。接下来，我们研究了YM53601产生的自由基的类型。鉴定出了高活性的羟基自由基。羟基自由基与SQS降解的关系目前正在研究中。