Site-Specific Functionalization of Peptides by Cooperative Catalysis

在化学系化学催化项目的支持下，波士顿学院的Masayuki Wasa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。可预测地破坏复杂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个关键，并将提供有关酶催化原理的重要信息。Wasa博士和他的研究团队设计了一种催化剂，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，并研究以天然蛋白酶不易实现的方式切割酰胺键的新方法。 Wasa博士的团队试图为这一挑战找到一个可推广的解决方案。Wasa博士和他的研究小组还参与了外展活动，通过为波士顿和布鲁克林的高中学生和教师提供实习计划，促进不同人群参与STEM学科。Masayuki Wasa博士和他的研究小组正在为该网站开发“沮丧”刘易斯酸/布朗斯台德碱基对催化剂-选择性切割多官能肽以获得难以通过已知方法形成且具有显著生物学和化学价值的片段。“受抑的”刘易斯酸/布朗斯台德碱催化剂体系是这些反应的目标，因为它们具有增加酰胺官能团的酸性朝向去质子化而不经历自猝灭的独特能力和朝向位点选择性醇解和水解调节的模块性。在这些研究中，正在探索各种各样的环状和非环状肽底物，包括结构尚未完全阐明的基于复杂肽的天然产物。这些选址性催化剂开发活动也为研究生、本科生和高中生提供了培训场所。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。

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.