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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，化学部的生命过程化学计划资助赖斯大学的Zachary Ball博士研究化学改变天然蛋白质的结构，功能和用途的新方法。在自然界中，蛋白质由22个氨基酸组成，它们具有不同的功能结构。如果蛋白质能够采用自然生物系统中未知的结构，它们可能会显示新的功能或新的自组装特性。然而，合成新的人造蛋白质仍然具有挑战性。该项目的重点是合成新的起始材料，可以控制人造蛋白质的结构，从而发挥功能。合成方法产生了新的，一般的解决方案，了解蛋白质结构，因此，该项目福尔斯属于NSF的大想法了解生命的规则。该项目整合了对高中学生和教师的外联工作。两个小组都在鲍尔实验室学习并参与化学研究。教师们也有机会开发新的教学工具，将化学研究和发现结合起来，从而确保向年轻学生广泛传播现代化学研究的价值和兴奋。蛋白质的选择性化学操作仍然具有挑战性。该项目将过渡金属催化剂与具有不同结构和反应性的硼酸试剂相结合，以开发一套用于天然蛋白质的光控捕获，操作和调节的方法。金属催化剂和硼酸的结构变化是一种强大的合成工具，可以开发多种互补的生物缀合方法。该研究利用了焦谷氨酸盐的独特和显着的反应性，焦谷氨酸盐是一些蛋白质的N-末端的天然存在和容易编码的翻译后修饰，在金属催化的反应中与硼酸试剂反应。这些研究为复杂蛋白质结合物的单步构建和测试新的有用的选择性范例开发了基本概念。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。