New Synthetic Methods for Building Chip Based Libraries

Washington University, Saint Louis MO

Investigators

Abstract

This work will continue the development of microelectrode arrays as tools for probing interactions between small molecule libraries and biological receptors. The use of the microelectrode arrays allows for interactions between small molecules and biological receptors to be probed in "real-time" without the need for the subsequent washing steps typical of current state-of-the-art methods. In this way, more accurate information can be gathered about the three dimensional binding preferences of the receptor being studied. During the upcoming budget period, new site-selective chemistry that extends the general synthetic capabilities of the arrays will be explored. This work is essential because it is the synthetic methodology available for building molecules proximal to the microelectrodes in an array that defines both types of molecules that can be synthesized on the arrays and the nature of the biological problems that can be studied using them. Efforts will also be made to develop new polymer coatings for the microelectrode arrays that are compatible with the synthetic methods being discovered, to design and synthesize new linkers for attaching molecules to the polymer coatings so that the members of a molecular library on the arrays can be readily characterized, and to optimize the signaling capabilities of microelectrode arrays. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Kevin D. Moeller of the Department of Chemistry at Washington University in St. Louis. Professor Moeller's research involves the development of electrochemical methods for synthesizing organic molecules and probing their biological activity. The long-range impact of the proposed work will be to greatly enhance our ability to map the three-dimensional binding motifs of therapeutic targets and more effectively guide the design of new ligands and potential therapeutic agents for them. In this effort, microelectrode arrays will be developed and employed as tools for following the interactions between molecules and their targeted receptors as they happen. Successful accomplishment of this project will have a positive impact on the pharmaceutical and biotechnology industries.