Uttam Tambar, Ph.D., a professor of biochemistry at UT Southwestern, has been awarded the 2026 Haberecht Wildhare-Idea Research Grant to pursue a new approach to drug discovery. The $30,000 award supports his proposal, titled “When the Target Builds the Inhibitor: Enzyme-Directed Assembly of Drugs,” which aims to use biological targets to help create their own inhibitors.
Traditional drug development typically involves testing thousands of pre-made molecules to find one that binds to a specific protein. Dr. Tambar’s strategy reverses this process. Instead of testing finished compounds, his lab plans to introduce small, reactive chemical fragments into a protein’s binding pocket.
Within that pocket, these fragments are guided to join together, forming a new molecule that fits the target well and can block its activity.
The research team, which includes postdoctoral researcher Melanie Rodriguez, Ph.D., will employ two distinct chemical strategies to test this concept. The first method utilizes dynamic covalent chemistry, allowing fragments to form reversible bonds, break them, and recombine until a stable molecule is created inside the protein.
The second approach uses photochemistry, where light energy drives the formation of new bonds between fragments only when they are positioned closely together within the binding pocket.
Dr. Tambar noted that while the concept may appear unconventional, it could alter how certain drugs are discovered in the future. The Haberecht Wildhare-Idea Research Grant is designed to fund speculative ideas that traditional funding sources might not support. The program honors the late Rolf Haberecht, Ph.D., M.B.A., a former Southwestern Medical Foundation Trustee and longtime supporter of the institution.
