Uridine Bisphosphonates Differentiate Phosphoglycosyl Transferase Superfamilies.

Complex bacterial glycoconjugates are essential for bacterial survival, and drive interactions between pathogens and symbionts, and their human hosts. Glycoconjugate biosynthesis is initiated at the membrane interface by phosphoglycosyl transferases (PGTs), which catalyze the transfer of a phosphosugar from a soluble uridine diphospho-sugar (UDP-sugar) substrate to a membrane-bound polyprenol-phosphate (Pren-P). Two distinct superfamilies of PGT enzymes, denoted as polytopic and monotopic, carry out this reaction but show striking differences in structure and mechanism. With the goal of creating non-hydrolyzable mimics (UBP-sugars) of the UDP-sugar substrates as chemical probes to interrogate critical aspects of these essential enzymes, we designed and synthesized a series of uridine bisphosphonates (UBPs), wherein the diphosphate bridging oxygen of the UDP and UDP-sugar is replaced by a substituted methylene group (CXY; X/Y = F/F, Cl/Cl, (

Déclaration de conflit d'intérêts

The authors declare no competing financial interest.