CAREER: Structure-selective protein modification with dirhodium metallopeptide catalysts

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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.