Quinone methide - based strategies for reversible modification, protection, and ligation of biological substrates and polymers

基于醌甲基化物的生物底物和聚合物的可逆修饰、保护和连接策略

• 批准号: 1565646
• 负责人: Vladimir Popik
• 金额: $ 48万
• 依托单位: University of Georgia Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1565646&HistoricalAwards=false
• 关键词: Quinone; methide; based; strategies; reversible

In this project funded by the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Vladimir Popik of the Department of Chemistry at the University of Georgia is developing new approaches for modifying the structures of biological molecules and materials using light. Methods utilizing light-directed reversible derivatization of biological molecules would allow one to control their properties in time and in space. Technological applications of such chemical methods may include drug delivery materials and protein engineering. This project provides students with an interdisciplinary training at the interface of synthetic chemistry, photochemistry, and biochemistry. High school students are conducting summer internships in the laboratory of Professor Popik through the University of Georgia Young Dawgs Program, and they are experiencing modern scientific research. With previous NSF support Professor Popik developed a new family of photolabile protecting groups and demonstrated the Diels-Alder and Michael reactivity of photo-generated o-quinone methides. The strategy incorporates several desirable features: the very fast release of a substrate, "bleaching" of the initial chromophore, and the generation of a fluorescent marker or a different color. Photochromic moieties add a built-in timer for photolabile protecting groups. Professor Popik and his group are designing and synthesizing new o-quinone methide precursors sensitive to long wavelengths of light. Also, they are further studying the mechanism of o-quinone methide formation and the pH-dependence of the thiol- quinone methide reaction kinetics. The pH-control of cysteine labeling allows for selective derivatization of these residues in multi-cysteine substrates, so they are applying these methods to the selective derivatization of proteins under different conditions (pH, light, competing nucleophiles) and examining the reversibility of the protein modification. Based upon this chemistry, Professor Popik is also exploring the feasibility of using o-quinone methide derivatives as protease inhibitors.

在化学结构，动态和机制B计划资助的该项目中，佐治亚大学化学系教授Vladimir Popik教授正在开发新的方法，以使用光使用光来修改生物分子和材料的结构。利用生物分子的光转导衍生化的方法将使人们在时间和太空中控制其性质。 这种化学方法的技术应用可能包括药物输送材料和蛋白质工程。该项目为学生提供了在合成化学，光化学和生物化学界面的跨学科培训。高中生正在通过佐治亚大学Young Dawgs计划在Popik教授实验室进行暑期实习，他们正在经历现代科学研究。 Popik教授以前的NSF支持教授开发了一个新的光片保护群体，并证明了光产生的O- Qu-Quyone甲基的Diels-Alder和Michael反应性。 该策略结合了几个理想的特征：底物的快速释放，初始发色团的“漂白”以及荧光标记或其他颜色的产生。 PhotoCromic部分添加了一个内置计时器，用于光片保护组。 Popik教授及其小组正在设计和合成对长波长光敏感的新的O-喹酮甲基前体。 同样，他们正在进一步研究甲酸甲酯形成的机理和硫醇 - 喹酮甲基反应动力学的pH依赖性。 半胱氨酸标记的pH-Control允许在多半胱氨酸底物中选择性地衍生这些残基，因此它们将这些方法应用于在不同条件（pH，光，竞争性核糖指数）下蛋白质的选择性衍生化，并检查蛋白质修饰的可持续性。 基于这种化学，Popik教授还探索了将O-喹酮甲基衍生物作为蛋白酶抑制剂的可行性。