Catalytic Protein Bioconjugation with Boronic Acid Reagents

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With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Zachary Ball from Rice University to investigate new ways to chemically change the structure, function, and use of natural proteins. In nature, proteins are built from 22 amino acids and they adopt structures that have diverse functions. If proteins could adopt structures unknown in natural biological systems, they may display new functions or new self-assembling properties. However, the synthesis of new man-made proteins remains challenging. The project focuses on the synthesis of new starting materials that can control the man-made protein structure, and thus function. The synthetic methods produce new, general solutions for understanding protein structure thus, the project falls under the NSF Big Idea Understanding the Rules of Life. The project integrates outreach efforts to high school students and teachers. Both groups learn about, and participate in, chemical research in the Ball laboratories. The teachers are also given the opportunity to develop new teaching tools that incorporate chemical research and discovery and thus, ensure the broad dissemination of the value and excitement of modern chemical research to young students.The selective chemical manipulation of proteins remains challenging. This project combines transition-metal catalysts with boronic acid reagents of diverse structure and reactivity to develop a suite of methods for the photo-controlled capture, manipulation, and regulation of natural proteins. Variation of the structure of both the metal catalyst and the boronic acid is a powerful synthetic tool that allows the development of diverse and complementary bioconjugation methods. The research exploits the unique and remarkable reactivity of pyroglutamate, which is a naturally-occurring and readily-encoded posttranslational modification of the N-terminus of some proteins, in metal-catalyzed reactions with boronic acid reagents. These studies develop fundamental concepts for single-step construction of complex protein conjugates and for testing new and useful selectivity paradigms.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.