CAREER: Structure-selective protein modification with dirhodium metallopeptide catalysts

有了这个职业奖，生命过程化学项目正在支持莱斯大学的Zachary Ball教授的研究。鲍尔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，对蛋白质进行基于邻近的化学修饰。这种方法的结果是基于形状和二级结构的催化活性，而不是固有的官能团反应性。鲍尔教授的方法将被用来表征多肽结合界面，这是基于金属镝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众多的生物信号过程，但研究起来很有挑战性。这种新的方法可能为传统的亲和标记和光亲和标记提供一种概念上的新选择，并有可能能够捕捉到更弱和/或更瞬时的蛋白质-蛋白质相互作用。从长远来看，这种类卡宾标记技术可能在化学生物学中有重要的应用，既可以识别给定探针配体的未知结合伙伴，也可能开始识别新的细胞信号或调控途径。该项目将作为一个平台，通过研究生培训和相关的教师培训计划，在拥有大量经济困难学生和传统上在科学界代表性较低的少数族裔的当地地区，培训未来的科学家。鲍尔教授将进行一项全面的教师培训计划，包括化学和化学教育方面的指导、研究经验和新课程开发。教师们将在PI的实验室里花一个夏天的时间进行研究，并根据他们的研究开发基于探究的课程。课程计划将通过在地区ACS会议上的演讲、休斯顿其他高中教师的研讨会以及通过网络进行传播。

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.