Catalytic Protein Bioconjugation with Boronic Acid Reagents

硼酸试剂催化蛋白质生物缀合

基本信息

批准号：
1904865
负责人：
Zachary Ball
金额：
$ 53.1万
依托单位：
William Marsh Rice University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1904865&HistoricalAwards=false
关键词：
Catalytic Protein Bioconjugation Boronic Acid

项目摘要

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Zachary Ball from Rice University to investigate new ways to chemically change the structure, function, and use of natural proteins. In nature, proteins are built from 22 amino acids and they adopt structures that have diverse functions. If proteins could adopt structures unknown in natural biological systems, they may display new functions or new self-assembling properties. However, the synthesis of new man-made proteins remains challenging. The project focuses on the synthesis of new starting materials that can control the man-made protein structure, and thus function. The synthetic methods produce new, general solutions for understanding protein structure thus, the project falls under the NSF Big Idea Understanding the Rules of Life. The project integrates outreach efforts to high school students and teachers. Both groups learn about, and participate in, chemical research in the Ball laboratories. The teachers are also given the opportunity to develop new teaching tools that incorporate chemical research and discovery and thus, ensure the broad dissemination of the value and excitement of modern chemical research to young students.The selective chemical manipulation of proteins remains challenging. This project combines transition-metal catalysts with boronic acid reagents of diverse structure and reactivity to develop a suite of methods for the photo-controlled capture, manipulation, and regulation of natural proteins. Variation of the structure of both the metal catalyst and the boronic acid is a powerful synthetic tool that allows the development of diverse and complementary bioconjugation methods. The research exploits the unique and remarkable reactivity of pyroglutamate, which is a naturally-occurring and readily-encoded posttranslational modification of the N-terminus of some proteins, in metal-catalyzed reactions with boronic acid reagents. These studies develop fundamental concepts for single-step construction of complex protein conjugates and for testing new and useful selectivity paradigms.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

有了这个奖项，化学司的化学过程计划正在为赖斯大学的Zachary Ball博士提供资金，以研究化学改变自然蛋白的结构，功能和使用的新方法。在本质上，蛋白质是由22种氨基酸建造的，它们采用具有多种功能的结构。如果蛋白质可以采用自然生物系统中未知的结构，它们可能会显示新功能或新的自组装特性。但是，新的人造蛋白质的合成仍然具有挑战性。该项目着重于可以控制人造蛋白质结构并因此起作用的新起始材料的合成。合成方法产生了新的一般解决方案，以理解蛋白质结构，因此该项目属于NSF的大思想，理解了生命规则。该项目将外展工作与高中生和老师相结合。两组都在鲍尔实验室学习并参与化学研究。还可以使教师有机会开发新的教学工具，以结合化学研究和发现，从而确保对年轻学生的现代化学研究价值和兴奋的广泛传播。对蛋白质的选择性化学操纵仍然具有挑战性。该项目将过渡金属催化剂与多种结构和反应性的硼酸试剂相结合，以开发一套用于光照控制的捕获，操纵和天然蛋白质调节的方法。金属催化剂和硼酸的结构的变化是一种强大的合成工具，可开发多种和互补的生物缀合方法。该研究利用了焦谷氨酸的独特而显着的反应性，这是一种天然蛋白质的N-末端的自然呈现的，很容易编码的翻译后修饰，在金属与硼酸反应的金属催化反应中。这些研究开发了用于单步构建复杂蛋白质结合物的基本概念，并测试了新的和有用的选择性范式。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子和更广泛影响的评估来评估的支持标准。