Achieving bacteriostasis using diamide inhibitors of bacterial GlcNAcases

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Title
Achieving bacteriostasis using diamide inhibitors of bacterial GlcNAcases
Contributors
Jamieson, Mitchell (creator)
Basu, Amit (advisor)
Brown University. LINK Award (research program)
Doi
10.26300/kzze-wy65
Date Created
2015-08-07
Abstract
Last year, the World Health Organization classified antimicrobial resistance as a "serious, worldwide threat to public health." Newly developed antibiotics must therefore circumvent the known mechanisms of bacterial resistance for better efficacy. The Basu Laboratory has discovered a new class of small molecules that inhibit bacterial cell wall recycling and remodeling enzymes that act on the invariable glycan backbone of the peptidoglycan heteropolymer. Several of these compounds have demonstrated bacteriostatic activity against Bacillus subtilis. The most potent inhibitors are dipeptides that were synthesized using the Ugi multicomponent condensation reaction. Resazurin whole cell assays have proven successful, and preliminary isothermal titration calorimetry experiments utilizing the enzyme target LytG (exo-acting GlcNAcase) are promising. With a large compound library in its third generation, we aim to improve the potency of these inhibitors through determination of which moieties hinder bacterial growth most.
Keywords
Drug resistance in microorganisms
Peptidoglycans
Resazurin
Extent
1 poster

Citation

Jamieson, Mitchell, "Achieving bacteriostasis using diamide inhibitors of bacterial GlcNAcases" (2015). Summer Research Symposium. Brown Digital Repository. Brown University Library. https://doi.org/10.26300/kzze-wy65

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