Carboxylate Surrogates Enhance the Antimycobacterial Activity of UDP-Galactopyranose Mutase Probes.

ABSTRACT: Uridine diphosphate galactopyranose mutase (UGM also known as Glf) is a biosynthetic enzyme required for construction of the galactan, an essential mycobacterial cell envelope polysaccharide. Our group previously identified two distinct classes of UGM inhibitors; each possesses a carboxylate moiety that is crucial for potency yet likely detrimental for cell permeability. To enhance the antimycobacterial potency, we sought to replace the carboxylate with a functional group mimic-an N-acylsulfonamide group. We therefore synthesized a series of N-acylsulfonamide analogs and tested their ability to inhibit UGM. For each inhibitor scaffold tested, the N-acylsulfonamide group functions as an effective carboxylate surrogate. Although the carboxylates and their surrogates show similar activity aga

SUBMITTER: Winton VJ 

PROVIDER: S-EPMC5745143 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature