In this project funded by the Macromolecular, Supramolecular and Nanochemistry Program of the Chemistry Division, Adam Urbach of Trinity University explores the hypothesis that the terminus of a polypeptide chain has unique structural and conformational properties that may provide a general approach to protein recognition that is specific to a single site and is predictable both from the sequence of amino acids and from the receptor's ability to recognize short peptides of the same sequence. The project has three complementary aims. The first aim focuses on the discovery and characterization of new motifs for the recognition of peptide termini by synthetic receptors. The second part asks whether these receptors can recognize proteins containing the same terminal sequences. The third part involves the application of the recognition work to the labeling, capture, and release of proteins using conjugates of the synthetic receptors to bring functionality to the terminus of the proteins targeted in these studies. In addition to the societal benefits of being able to identify, isolate, and label specific proteins, the broader impacts involve intense training of undergraduate students in the research laboratory and a plan for the training of postdoctoral scholars that addresses crucial aspects of professional development in scholarship, teaching, and service in order to best prepare them to begin a career at a primarily undergraduate institution.
The ability to distinguish between the numerous proteins in living systems is crucial to biological and biotechnological processes, but currently only antibodies can do this reliably and antibody-based technology can be very costly. This research aims to address this problem by developing new methods for interacting with proteins using synthetic receptors, which can be much less expensive and easier to modify. The focus of this project is to explore the recently developed concept that the very end of a protein chain (the terminus) is an ideal site for interacting with a receptor because the tail, like the end of a ball of string, can easily unravel. If successful, this research would establish a general method for predictably interacting with proteins, and it would form the foundation for developing tools that substantially improve our understanding of protein function in living systems.
