%0 Journal Article %A Winton, Valerie J. %A Aldrich, Claudia %A Kiessling, Laura L. %D 2016 %T Carboxylate Surrogates Enhance the Antimycobacterial Activity of UDP-Galactopyranose Mutase Probes %U https://acs.figshare.com/articles/journal_contribution/Carboxylate_Surrogates_Enhance_the_Antimycobacterial_Activity_of_UDP-Galactopyranose_Mutase_Probes/3545994 %R 10.1021/acsinfecdis.6b00021.s001 %2 https://acs.figshare.com/ndownloader/files/5611176 %K mycobacterial cell envelope polysaccharide %K Carboxylate Surrogates Enhance %K UGM %K carboxylate %K potency %K antimycobacterial %K acylsulfonamide group %K acylsulfonamide group functions %K inhibitor %X 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 against UGM in a test tube, several N-acylsulfonamide derivatives more effectively block the growth of Mycobacterium smegmatis. These data suggest that the replacement of a carboxylate with an N-acylsulfonamide group could serve as a general strategy to augment antimycobacterial activity. %I ACS Publications