Steve Withers

June 10, 2010:

 

 

Design and selection of glycosidase inhibitors towards therapies for Diabetes, Influenza and Gaucher disease

University of British Columbia, Department of Biochemistry, http://www.chem.ubc.ca/personnel/faculty/withers/group/

 

Carbohydrates play important roles in biological systems, not only in the form of energy storage materials such as starch, but also as “recognition elements” on cell surfaces. The synthesis and degradation of such sugar structures is achieved using enzymes known as glycosyl transferases and glycoside hydrolases (glycosidases) respectively. Specific enzyme inhibitors are not only useful tools for understanding enzyme mechanisms, but also can play important roles as therapeutics if inhibition suppresses unwanted reactions. This will be illustrated with examples from our own work. One concerns the use of designed mechanism-based inhibitors as potential therapeutics for influenza, through inhibition of the viral neuraminidase. In a second example I shall show how high-throughput screening of natural product libraries has yielded potent inhibitors of human a-amylase that are showing useful potential in control of blood glucose levels in diabetic rats. Finally I shall present recent work on the use of mechanism-based inhibitors as PET imaging probes to monitor enzyme replacement therapy for Gaucher disease.

 

Pictures of the event