Tetrafluorination of Sugars as Strategy for Enhancing Protein–Carbohydrate Affinity: Application to UDP‐Gal<i>p</i> Mutase Inhibition

Abstract

Tetrafluorinated analogues of both UDP-galactopyranose and UDP-galactofuranose have been synthesized and assayed against UDP-galactopyranose mutase, a key enzyme for Mycobacterium tuberculosis cell wall biosynthesis. Competition assays and STD-NMR spectroscopy techniques have evidenced not only the first unambiguous case of affinity enhancement through local sugar polyfluorination, but also showed that tetrafluorination can still have a beneficial effect on binding when monofluorination at the same position does not.