Our research program is focused in the areas of synthetic chemistry (with a particular emphasis in carbohydrate chemistry), the conformational analysis of oligosaccharides and the design of novel therapeutic agents that act by inhibiting carbohydrate-processing enzymes. Students and postdoctoral fellows in the group use synthetic chemistry to prepare compounds with interesting biological activities and then have the opportunity to use them in either biochemical or conformational studies.
The primary research focus is directed ultimately towards the identification of new drugs for the treatment of tuberculosis. Our approach is to develop inhibitors of the enzymes that assemble the polysaccharide portions of the protective cell wall of the organism responsible for this disease, Mycobacterium tuberculosis. These polysaccharides are unique in that they are comprised largely of monosaccharides in the furanose ring form. The synthesis of these compounds has been largely neglected by synthetic chemists and our efforts involve both total synthesis and the development of new synthetic methods.
We have completed the total synthesis of a 22-residue oligosaccharide that is an important motif found in the mycobacterial cell wall and fragments of this oligosaccharide, and related analogues, are currently being synthesized and explored in the development of novel vaccines for the prevention of tuberculosis. We are also working towards the characterization of glycosyltransferases involved in mycobacterial cell wall biosynthesis.