CARB 14 |
| Cells that have undergone oncogenic transformation often display abnormal cell surface oligosaccharides. These changes in glycosylation are important determinants of the stage, direction and fate of tumor progression. The inhibition of the mannose trimming enzyme human Golgi alpha-mannosidase II (HGMII), which acts late in the N-glycan processing pathway, provides one route to blocking the oncogene-induced changes in cell surface oligosaccharide structures. A serious side effect of most mannosidase inhibitors is, however, the blockage in oligosaccharide catabolism arising from the inhibition of a related catabolic alpha-mannosidase found in lysosomes. The development of a drug appropriate for anti-metastatic therapy requires a compound that specifically inhibits Golgi alpha-mannosidase II without affecting the function of lysosomal alpha-mannosidase (HLM). We report here several strategies to improve the selectivity of mannosidase inhibitors. |
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Hudson Award Symposium
8:30 AM-12:00 PM, Monday, 14 March 2005 San Diego Marriott -- San Diego A, Oral
Division of Carbohydrate Chemistry |