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8 results on '"Bradley Wolfe"'

1. Multi-Probe 23A: Post shot Data and Analysis

Author

Chun-Shang Wong, Mariana Alvarado Alvarez, Steven Batha, David Broughton, Chengkun Huang, Harold Jorgenson, Robert Reinovsky, Thomas Schmidt, Zhehui Wang, Carl Wilde, Bradley Wolfe, and Benjamin Wyatt

Published
2023

4. Discovery of Novel Putative Inhibitors of UDP-GlcNAc 2-Epimerase as Potent Antibacterial Agents

Author

Steve Warner, C. Erec Stebbins, Bhasker Aavula, Adam J. Pelzek, Vincent A. Fischetti, Bhaskaran Shyam S, Michael V. McCullar, Chongtie Shi, Yong Xu, Jared Bearss, David J. Bearss, Allan R. Goldberg, Adrianne Clifford, Bradley Wolfe, Carissa Jones, David Vollmer, Hariprasad Vankayalapati, Virgil McCarthy, Raymond Schuch, and Benjamin Brenning

Subjects
Virtual screening, biology, business.industry, medicine.drug_class, Gram-positive bacteria, Organic Chemistry, Antibiotics, Rational design, Epimerox, biology.organism_classification, Biochemistry, Microbiology, chemistry.chemical_compound, Minimum inhibitory concentration, chemistry, In vivo, Drug Discovery, Medicine, business, Antibacterial agent
Abstract

We present the discovery and optimization of a novel series of inhibitors of bacterial UDP-N-acetylglucosamine 2-epimerase (called 2-epimerase in this paper). Starting from virtual screening hits, the activity of various inhibitory molecules was optimized using a combination of structure-based and rational design approaches. We successfully designed and identified a 2-epimerase inhibitor (compound 12-ES-Na, that we named Epimerox) which blocked the growth of methicillin-resistant Staphylococcus aureus (MRSA) at 3.9 μM MIC (minimum inhibitory concentration) and showed potent broad-range activity against all Gram-positive bacteria that were tested. Additionally a microplate coupled assay was performed to further confirm that the 2-epimerase inhibition of Epimerox was through a target-specific mechanism. Furthermore, Epimerox demonstrated in vivo efficacy and had a pharmacokinetic profile that is consonant with it being developed into a promising new antibiotic agent for treatment of infections caused by Gram-positive bacteria.

Published
2013

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