Site-Specific Functionalization of Peptides by Cooperative Catalysis

在化学系化学催化计划的支持下，波士顿学院的Masayuki Wasa博士正在开发非天然催化剂，目标是模拟蛋白酶的酶活性，并选择性地将多肽切割在特定的酰胺键上。预测断裂复杂多肽结构中的特定酰胺键的能力将是仿生催化剂开发中的一大亮点，并将提供关于酶催化原理的重要信息。瓦萨博士和他的研究团队设计的催化剂可以同时激活酸性基团和碱性基团，而不会相互反应。在这个项目中，他们正在进一步开发这种催化技术，以模拟酶中活性位点的空间差异，并研究以自然产生的蛋白酶酶不易实现的方式裂解酰胺键的新方法。瓦萨博士的团队试图为这一挑战找到一种通用的解决方案。瓦萨博士和他的研究小组还参与了外联活动，通过波士顿和布鲁克林高中的学生和教师实习计划，在不同人群中促进与STEM学科的接触。Masayuki Wasa和他的研究小组正在开发“受挫”的Lewis酸/Bronsted碱基对催化剂，用于对多功能多肽进行位点选择性切割，以获得用已知方法难以形成的具有重大生物和化学价值的片段。“受挫”的Lewis酸/Bronsted碱催化剂系统是这些反应的目标，因为它们具有独特的能力，可以增加酰胺官能团的酸性，从而在不发生自猝灭的情况下实现去质子化，并具有可调节的模块化，以实现位置选择性的醇解和水解。在这些研究中，人们正在探索一系列不同的环肽和非环肽底物，包括基于复杂多肽的天然产物，其结构尚未完全阐明。这些现场选择性催化剂开发活动也是研究生、本科生和高中生不同群体的培训基地。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.