Inhibition of glycoprotein biosynthesis in the pathogenic bacterium <i>Helicobacter pylori</i> by masked carbohydrate phosphonates.

ABSTRACT: The glycan-rich surface of Helicobacter pylori plays a critical role in host-pathogen interactions and represents a promising target for therapeutic intervention. We report the synthesis and biological evaluation of a masked bis(pivaloyloxymethyl) phosphonate analogue of α-D-glucose 1-phosphate designed to inhibit glycoprotein biosynthesis in H. pylori. This prodrug strategy enhances bacterial uptake by neutralizing the phosphonate's dianionic charge, potentially enabling intracellular esterase-mediated release of the active phosphonate. Using metabolic oligosaccharide engineering (MOE) with Ac₄GlcNAz, we demonstrate that the masked phosphonate exhibits dose-dependent inhibition of glycoprotein biosynthesis, whereas unmasked and cyclic phosphonate analogues show mi

SUBMITTER: Soleimani E 

PROVIDER: S-EPMC12681240 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature