Achieving bacteriostasis using diamide inhibitors of bacterial GlcNAcases


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.


Jamieson, Mitchell, "Achieving bacteriostasis using diamide inhibitors of bacterial GlcNAcases" (2015). Summer Research Symposium. Brown Digital Repository. Brown University Library.



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    Each year, Brown University showcases the research of its undergraduates at the Summer Research Symposium. More than half of the student-researchers are UTRA recipients, while others receive funding from a variety of Brown-administered and national programs and fellowships and go …