报告题目：Design and selection of glycosidase inhibitors towards therapies for Diabetes and Influenza
报 告 人：Stephen G. Withers
联 系 人：杨广宇 021-34207248
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 and synthesized mechanism-based inhibitors as potential therapeutics for influenza, through inhibition of the viral neuraminidase1. In a second example I shall show how high-throughput screening of natural product extract libraries has yielded potent inhibitors of human a-amylase that are showing useful potential in control of blood glucose levels in diabetic rats2.
1. Kim, J-H, Resende, R., Wennekes, T., Chen, H., Bance, N., Buchini, S., Watts, A. G., Pilling, P., Streltsov, V. A., Petric, M., Liggins, R., Barrett, S., McKimm-Breschkin, J. L., Niikura, M. and Withers, S. G. “Mechanism-based Covalent Neuraminidase Inhibitors with Broad Spectrum Influenza Antiviral Activity” (2013) Science, 340, 71-75.
2. Tarling, C. A., Woods, K., Brastianos, H. C., Zhang, R., Brayer, G. D., Andersen, R. J. and Withers, S. G. “The Search for Novel Human Pancreatic a-Amylase Inhibitors: High-Throughput Screening of Terrestrial and Marine Natural Product Extracts” (2008) ChemBioChem. 9, 433-438.