Rational Design Of Cell Active C2-Modified Dgj Analogues For The Inhibition Of Human Alpha-Galactosidase A (Gala)

We report the rational design and synthesis of C2-modified DGJ analogues to improve the selective inhibition of human GALA over other glycosidases. We prepare these analogues using a concise route from non-carbohydrate materials and demonstrate the most selective inhibitor 7c (similar to 100-fold) can act in Fabry patient cells to drive reductions in levels of the disease-relevant glycolipid Gb3.