CAREER: Structure-selective protein modification with dirhodium metallopeptide catalysts

“生命过程化学”项目通过这一职业奖，支持了莱斯大学扎卡里·鲍尔教授的研究。Ball教授正在开发一种新的概念，通过超分子化学和有机金属催化的新组合，以接近为基础的蛋白质化学修饰。这种方法产生的催化活性基于形状和二级结构，而不是固有的官能团反应性。Ball教授的方法将用于多肽结合界面的表征，该方法基于金属多肽将瞬时结合转化为共价修饰的能力。蛋白质之间短暂的相互作用控制着许多生物信号过程，但研究起来具有挑战性。新方法可能为传统的亲和标记和光亲和标记提供概念上新颖的替代方案，并且可能能够捕获较弱和/或更瞬态的蛋白质-蛋白质相互作用。从长远来看，这种类rh碳标签技术在化学生物学中有重要的应用，既可以识别未知的探针配体的结合伙伴，也可以开始识别新的细胞信号传导或调节途径。该项目将成为培养未来科学家的平台，既可以通过研究生培训，也可以通过在当地地区开展教师培训项目，这些地区有大量经济困难的学生和传统上在科学领域代表性不足的少数民族。鲍尔教授将开展一项全面的教师培训计划，包括化学和化学教育教学、研究经验和新课程开发。教师们将花一个夏天在PI的实验室进行研究，并根据他们的研究开发探究式课程。课程计划将通过区域ACS会议的谈话、休斯顿其他高中教师的讲习班以及网络传播。

With this CAREER Award, the Chemistry of Life Processes Program is supporting the research of Professor Zachary Ball of Rice University. Professor Ball is developing a new concept for the proximity-based chemical modification of proteins through a new combination of supramolecular chemistry and organometallic catalysis. This approach results in catalytic activity based on shape and secondary structure rather than inherent functional group reactivity. Professor Ball's method will be used to characterize polypeptide binding interfaces, based on the ability of dirhodium metallopeptides to convert transient binding into covalent modification. Fleeting interactions between proteins govern numerous biological signaling processes, yet are challenging to study. The new approach may provide a conceptually novel alternative to traditional affinity-labeling and photo-affinity labeling, and potentially one that will be able to capture weaker and/or more transient protein-protein interactions.This Rh-carbenoid labeling technique could have important applications in chemical biology, in the longer term, both to identify as yet unknown binding partners for a given probe ligand, and to potentially even begin to identify new cellular signaling or regulatory pathways. The project will serve as a platform to train future scientists, both through graduate student training and through affiliated teacher-training programs in local districts with significant populations of economically disadvantaged students and of minorities traditionally underrepresented in the sciences. Professor Ball will conduct a comprehensive teacher-training program consisting of instruction in chemistry and chemical education, research experience, and new curriculum development. Teachers will spend a summer in the PI's lab to conduct research and to develop inquiry-based lessons based on their research. Lesson plans will be disseminated through talks at regional ACS meetings, workshops for other high school teachers in Houston, and via the web.