alpha-Bromophosphonate analogs of glucose-6-phosphate are inhibitors of glucose-6-phosphatase

作者：Downey A Michael; Cairo Christopher W^*

来源：Carbohydrate Research, 2013, 381: 123-132.

DOI：10.1016/j.carres.2013.08.003

• Glucose-6-phosphate (G6P)
• Glucose-6-phosphatase (G6Pase)
• Non-hydrolyzable phosphate isostere
• alpha-Bromophosphonate

Glucose-6-phosphatase (G6Pase) is an essential metabolic enzyme that has upregulated activity in Type II diabetes. Synthetic analogs of the G6Pase substrate, glucose-6-phosphate (G6P), may provide new tools to probe enzyme activity, or lead to specific inhibitors of glycosylphosphatase enzymes. Here we have developed synthetic routes to a panel of non-hydrolyzable G6P analogs containing alpha-bromo,alpha,alpha-dibromo, and alpha-bromo-alpha, beta-unsaturated phosphonates compatible with a carbohydrate nucleus. We confirm that these functionalities have potency as inhibitors of G6Pase in vitro, providing a series of new phosphate isosteres that can be exploited for inhibitor design.

• 出版日期2013-11-15