Site-Specific Functionalization of Peptides by Cooperative Catalysis

通过协同催化对肽进行位点特异性功能化

• 批准号: 2341523
• 负责人: Masayuki Wasa
• 金额: $ 47.5万
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2341523&HistoricalAwards=false
• 关键词: Site; Specific; Functionalization; Peptides; Cooperative

With the support of the Chemical Catalysis Program in the Division of Chemistry, Dr. Masayuki Wasa of Boston College is developing non-natural catalysts with the goal of mimicking protease enzyme activity and selectively cleaving peptides at specific amide bonds. The ability to predictably break specific amide bonds in complex peptide structures would be a tour de force in biomimetic catalyst development and would provide important information about the principles underlying enzymatic catalysis. Dr. Wasa and his research team have designed catalysts that can activate acidic and basic groups simultaneously without reacting with each other. In this project, they are further developing this catalytic technology to mimic the spatial differentiation of active sites in enzymes and investigating new ways to cleave amide bonds in ways that are not easily achievable with naturally occurring protease enzymes. Dr. Wasa's team seeks to achieve a generalizable solution to this challenge. Dr. Wasa and his research group are also involved in outreach activities to promote engagement with STEM disciplines among diverse populations through internship programs for students and teachers from high schools in Boston and Brookline.Dr. Masayuki Wasa and his research group are developing “frustrated” Lewis acid/Bronsted base pair catalysts for the site-selective cleavage of polyfunctional peptides to access fragments that are difficult to form by known methods and have significant biological and chemical value. “Frustrated” Lewis acid/Bronsted base catalyst systems are being targeted for these reactions because they have the unique ability to increase the acidity of the amide functionalities towards deprotonation without undergoing self-quenching and the modularity to be tuned toward site-selective alcoholysis and hydrolysis. A diverse array of cyclic and acyclic peptide substrates are being explored in these studies, including complex peptide-based natural products whose structures have not been fully elucidated. These site-selective catalyst development activities are also serving as a training ground for a diverse group of graduate, undergraduate, and high school students.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.

在化学系化学催化项目的支持下，波士顿学院的Wasa Masayuki博士正在开发非天然催化剂，其目标是模拟蛋白酶的活性，并在特定的酰胺键上选择性地切割肽。在复杂肽结构中可预测地破坏特定酰胺键的能力将是仿生催化剂开发中的一个力作，并将提供有关酶催化原理的重要信息。Wasa博士和他的研究小组设计了一种催化剂，可以同时激活酸性和碱性基团，而不会相互反应。在这个项目中，他们正在进一步发展这种催化技术，以模拟酶中活性位点的空间分化，并研究以自然存在的蛋白酶难以实现的方式切割酰胺键的新方法。Wasa博士的团队试图找到一种通用的解决方案来应对这一挑战。Wasa博士和他的研究小组还参与了外展活动，通过波士顿和布鲁克林高中的学生和教师实习项目，促进不同人群对STEM学科的参与。Masayuki Wasa和他的研究小组正在开发“挫折”Lewis酸/Bronsted碱基对催化剂，用于多能肽的位点选择性切割，以获得难以用已知方法形成的具有重要生物和化学价值的片段。“受挫”的Lewis酸/Bronsted碱催化剂体系之所以成为这些反应的目标，是因为它们具有独特的能力，可以在不经历自淬灭的情况下增加酰胺官能团的酸度，从而实现去质子化，并且模块化可以调整为选择性醇解和水解。在这些研究中，各种各样的环和无环肽底物正在被探索，包括结构尚未完全阐明的复杂肽基天然产物。这些选择性催化剂开发活动也为研究生、本科生和高中生提供了一个训练基地。该奖项反映了美国国家科学基金会的法定使命，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。