Carboxylate Surrogates Enhance the Antimycobacterial
Activity of UDP-Galactopyranose Mutase Probes
Valerie J. Winton
Claudia Aldrich
Laura L. Kiessling
10.1021/acsinfecdis.6b00021.s001
https://acs.figshare.com/articles/journal_contribution/Carboxylate_Surrogates_Enhance_the_Antimycobacterial_Activity_of_UDP-Galactopyranose_Mutase_Probes/3545994
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 mimican <i>N</i>-acylsulfonamide group. We therefore synthesized a series of <i>N</i>-acylsulfonamide analogs and tested their ability to inhibit
UGM. For each inhibitor scaffold tested, the <i>N</i>-acylsulfonamide
group functions as an effective carboxylate surrogate. Although the
carboxylates and their surrogates show similar activity against UGM
in a test tube, several <i>N</i>-acylsulfonamide derivatives
more effectively block the growth of <i>Mycobacterium smegmatis</i>. These data suggest that the replacement of a carboxylate with an <i>N</i>-acylsulfonamide group could serve as a general strategy
to augment antimycobacterial activity.
2016-06-16 00:00:00
mycobacterial cell envelope polysaccharide
Carboxylate Surrogates Enhance
UGM
carboxylate
potency
antimycobacterial
acylsulfonamide group
acylsulfonamide group functions
inhibitor