Grant: Discovery Grants Program - Individual

The detailed chemical interactions that occur between molecules are important in how molecules recognize, bind to and even alter other molecules, including metals. These interactions occur every time two molecules encounter each other such as when a pharmaceutical drug binds to a biological site on a human cell. In addition, these interactions are used by a variety of inorganic and biological (enzyme) catalysts to produce chemical change in materials. Our research attempts to add to our fundamental knowledge in this area by studying and probing these interactions at the biochemical level. Investigations into the parameters important for protein structure and protein-substrate, protein-metal and protein-protein interactions are being undertaken in our project. As well, we are concerned with the application of chemistry to understanding how biochemical catalysts (enzymes) specifically bind and rapidly catalyze chemical reactions. This type of information, although fundamental, has very broad implications in biochemistry and in the pharmaceutical area where the knowledge of a chemical mechanism of an enzyme in a pathogenic organism could be utilized to provide a molecular Achilles heel for the development of new drugs. Our particular approach has also required that we be able to introduce our chemical probes into the macromolecule itself, and so, as chemists, we have had to also learn the language and techniques of molecular biology. The ability of chemistry to provide tailor-made molecules to serve as tools in probing biological processes is critical to our goal of understanding biochemical systems in terms of chemical structure. In essence, this research program utilizes a combined chemical and biochemical approach to probe the importance of the carbon-sulfur bond in biological systems. New discoveries in these areas are expected to ameliorate our fundamental knowledge of molecular recognition events, chemical mechanisms of enzymes and the underlying chemistry of metal selection and activation by proteins.