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Jung ME, Chamberlain BT, Ho CL, et al. Structure-Activity Relationship of Semicarbazone EGA Furnishes Photoaffinity Inhibitors of Anthrax Toxin Cellular Entry. ACS Med Chem Lett. 2014;5(4):363-7doi: 10.1021/ml400486k.
Jung, M. E., Chamberlain, B. T., Ho, C. L., Gillespie, E. J., & Bradley, K. A. (2014). Structure-Activity Relationship of Semicarbazone EGA Furnishes Photoaffinity Inhibitors of Anthrax Toxin Cellular Entry. ACS medicinal chemistry letters, 5(4), 363-7. https://doi.org/10.1021/ml400486k
Jung, Michael E, et al. "Structure-Activity Relationship of Semicarbazone EGA Furnishes Photoaffinity Inhibitors of Anthrax Toxin Cellular Entry." ACS medicinal chemistry letters vol. 5,4 (2014): 363-7. doi: https://doi.org/10.1021/ml400486k
Jung ME, Chamberlain BT, Ho CL, Gillespie EJ, Bradley KA. Structure-Activity Relationship of Semicarbazone EGA Furnishes Photoaffinity Inhibitors of Anthrax Toxin Cellular Entry. ACS Med Chem Lett. 2014 Jan 21;5(4):363-7. doi: 10.1021/ml400486k. eCollection 2014 Apr 10. PMID: 24900841; PMCID: PMC4027791.
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ACS Med Chem Lett. 2014 Jan 21;5(4):363-7. doi: 10.1021/ml400486k. eCollection 2014 Apr 10.

Structure-Activity Relationship of Semicarbazone EGA Furnishes Photoaffinity Inhibitors of Anthrax Toxin Cellular Entry.

ACS medicinal chemistry letters

Michael E Jung, Brian T Chamberlain, Chi-Lee C Ho, Eugene J Gillespie, Kenneth A Bradley

Affiliations

  1. California NanoSystems Institute, Department of Chemistry and Biochemistry, Department of Microbiology, Immunology and Molecular Genetics, University of California , Los Angeles, Los Angeles, California 90095, United States.

PMID: 24900841 PMCID: PMC4027791 DOI: 10.1021/ml400486k

Abstract

EGA, 1, prevents the entry of multiple viruses and bacterial toxins into mammalian cells by inhibiting vesicular trafficking. The cellular target of 1 is unknown, and a structure-activity relationship study was conducted in order to develop a strategy for target identification. A compound with midnanomolar potency was identified (2), and three photoaffinity labels were synthesized (3-5). For this series, the expected photochemistry of the phenyl azide moiety is a more important factor than the IC50 of the photoprobe in obtaining a successful photolabeling event. While 3 was the most effective reversible inhibitor of the series, it provided no protection to cells against anthrax lethal toxin (LT) following UV irradiation. Conversely, 5, which possessed weak bioactivity in the standard assay, conferred robust irreversible protection vs LT to cells upon UV photolysis.

Keywords: Photoaffinity labeling; anthrax lethal toxin; aryl azide; endosomal trafficking; semicarbazone

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