CAREER: MECHANISTIC BASIS OF AFFINITY ENHANCEMENT

Stanford University, Stanford CA

Investigators

Abstract

This project involves a range of educational activities that will continue to build a solid foundation for further contributions to teaching and research. The specific focus of the research component is to develop a novel method to improve binding of small organic molecules to their target proteins. Synthetic chemistry is used to construct bifunctional molecules which are capable of binding to two different proteins, whereupon additional stabilizing interactions may be acquired. Mechanistic studies are proposed to directly examine the trimeric complexes in solution, including high-resolution mass spectrometry and NMR spectroscopy. With this CAREER Award the Organic and Macromolecular Chemistry Program's Organic Dynamics Program supports the integrated research and educational activities of Professor Thomas J. Wandless of Stanford University. The proposed research will be used to take an observation from Nature (binding of small molecules with proteins to form bioactive complexes) to its recapitulation in the laboratory. This will provide biological and medicinal chemists with another tool in the ongoing search for biologically active and useful molecules. Activities are planned that contribute to curriculum development and improved student mentoring, including an outreach program for beginning organic chemistry students to promote improved mentoring and self-directed learning through research.