Structural-based inhibitors of the glutathione binding site in aldose reductase, methods of screening therefor and methods of use

摘要

Provided herein is a crystallized ternary structure of aldose reductase (AR) bound to NADPH and gamma-glutamyl-S-(1,2-dicarboxyethyl)cysteinylglycine (DCEG). Also provided are specific inhibitors of glutathione-aldehyde binding to aldose reductase which are designed via at least computer modeling of the ternary AR:NADPH:DCEG structure and methods of designing and of screening the inhibitors for inhibition of glutathione-aldehyde binding to aldose reductase.