Boronic Acid Methods for Chemical Manipulation of Biomacromolecules

硼酸化学操作生物大分子的方法

• 批准号: 2203948
• 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: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2203948&HistoricalAwards=false
• 关键词: Boronic; Acid; Methods; Chemical; Manipulation

With the support of the Chemistry of Life Processes (CLP) Program in the Division of Chemistry, Professor Zachary Ball from Rice University is studying selective chemical reactions in complex biological environments. The experiments will seek to understand how to design reactions to manipulate the atomic structure of proteins, using a combination of reaction design and novel screening approaches. Reaction design in complex environments remains challenging, but successful development of methods for the preparation of chemically modified proteins would have numerous beneficial applications. Hybrid or chemically-modified biologics are increasingly important classes of new drugs, and these molecules find use as molecular probes to better understand biological function, or as “smart” responsive soft materials. The project will integrate outreach efforts to expose local high school students to modern scientific research. Research experiences for high school science teachers are an important component of this project and serve to more widely disseminate the value and excitement of modern chemical research. With this support, the Rice research team will explore the unique properties of boronic acids to facilitate selective bioconjugation in several research objectives. Because polypeptides are polyfunctional environments with few uniquely reactive sites, it becomes necessary to pursue novel approaches to selectivity. Efforts will explore new directions in an ongoing program to design metal-catalyzed pathways with biocompatible boronic acid reagents for manipulating protein structure. First, boronic acids will be examined as cross-coupling reagents for new C–C and C–X bond formation, focusing in particular on the remarkable and unique reactivity of pyroglutamate-histidine sequences to enable one-step construction of protein-containing macromolecular conjugates and nano-objects without the need for secondary bioconjugation. Second, boronic acid–catalyst conjugates will be investigated as catalysts for the modification of glycoproteins and polysaccharides, based on dynamic covalent chemistry of boronic ester formation with hydroxy-rich regions to template proximity-driven reactivity, a novel approach to selective chemistry for oligosaccharide-containing structures. Complementary outreach efforts are designed to improved lay understanding of this exciting and important field of interdisciplinary research, and also to encourage, nurture, and motivate the next generation of researchers.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.

在化学系生命过程化学（CLP）项目的支持下，莱斯大学的Zachary Ball教授正在研究复杂生物环境中的选择性化学反应。这些实验将试图了解如何设计反应来操纵蛋白质的原子结构，使用反应设计和新的筛选方法相结合。复杂环境中的反应设计仍然具有挑战性，但成功开发制备化学修饰蛋白质的方法将具有许多有益的应用。混合或化学修饰的生物制剂是越来越重要的一类新药，这些分子可用作分子探针以更好地了解生物功能，或用作“智能”响应软材料。该项目将结合外联工作，使当地高中生接触现代科学研究。高中科学教师的研究经验是这个项目的重要组成部分，并有助于更广泛地传播现代化学研究的价值和兴奋。在此支持下，Rice研究团队将探索硼酸的独特性质，以促进几个研究目标的选择性生物缀合。由于多肽是多功能环境，独特的反应位点很少，因此有必要寻求新的选择性方法。努力将探索新的方向，在一个正在进行的计划，设计金属催化的途径与生物相容性硼酸试剂操纵蛋白质结构。首先，硼酸将作为新的C-C和C-X键形成的交叉偶联试剂进行检查，特别关注焦谷氨酸-组氨酸序列的显着和独特的反应性，以实现含蛋白质的大分子缀合物和纳米物体的一步构建，而不需要二次生物缀合。其次，硼酸催化剂共轭物将被研究作为催化剂的糖蛋白和多糖的修饰，基于动态共价化学硼酸酯形成与羟基丰富的区域模板邻近驱动的反应性，一种新的方法来选择性化学含寡糖的结构。该奖项旨在提高公众对这一令人兴奋和重要的跨学科研究领域的理解，并鼓励、培养和激励下一代研究人员。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。

项目成果

Dual-Boronic Acid Reagents That Combine Dynamic and Covalent Bioconjugation

结合动态和共价生物共轭的双硼酸试剂

• DOI: 10.1021/acs.bioconjchem.2c00508
• 发表时间: 2022
• 期刊: Bioconjugate Chemistry
• 影响因子: 4.7
• 作者: Swierczynski, Michael J.;Ding, Yuxuan;Ball, Zachary T.
• 通讯作者: Ball, Zachary T.

Polyol recognition in catalysis: Toward selective modification of glycosylated polypeptides with boronic acid-rhodium(II) catalysts

催化中的多元醇识别：用硼酸-铑(II)催化剂选择性修饰糖基化多肽

• DOI: 10.1039/d3cc03371f
• 发表时间: 2023
• 期刊: Chemical Communications
• 影响因子: 4.9
• 作者: Vargas, Reyner D.;Ding, Yuxuan;Trial, Hallie O.;Qian, Ruoyu;Ball, Zachary Thomas
• 通讯作者: Ball, Zachary Thomas