Antimicrobial Prodrug Activation by the Staphylococcal Glyoxalase GloB.

  title={Antimicrobial Prodrug Activation by the Staphylococcal Glyoxalase GloB.},
  author={Marwa O. Mikati and Justin J. Miller and Damon M. Osbourn and Yasaman Barekatain and Naomi Ghebremichael and Isha Shah and Carey-Ann D. Burnham and Kenneth M. Heidel and Victoria C. Yan and Florian L. Muller and Cynthia S. Dowd and Rachel L. Edwards and Audrey R. Odom John},
  journal={ACS infectious diseases},
With the rising prevalence of multidrug resistance, there is an urgent need to develop novel antibiotics. Many putative antibiotics demonstrate promising in vitro potency but fail in vivo due to poor drug-like qualities (e.g., serum half-life, oral absorption, solubility, and toxicity). These drug-like properties can be modified through the addition of chemical protecting groups, creating "prodrugs" that are activated prior to target inhibition. Lipophilic prodrugging techniques, including the… 
3 Citations
Structure-guided microbial targeting of antistaphylococcal prodrugs
The identifies the bacterial esterases, GloB and FrmB, that are required for carboxy ester prodrug activation in Staphylococcus aureus and establishes the substrate specificities of human and mouse sera, which lay the groundwork for structure-guided design of anti-staphyloccal promoieties and expand the range of molecules to target staphylOCcal pathogens.
Structure-guided microbial targeting of antistaphylococcal prodrugs
This work identifies the bacterial esterases, GloB and FrmB, that activate carboxy ester prodrugs in Staphylococcus aureus and establishes the substrate specificities of human and mouse sera, ultimately identifying several promoieties likely to be serum esterase-resistant and microbially labile.
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