Small molecule inhibitors of anthrax edema factor

Content Provider	Scilit
Author	O'Malley, Sean Jiao, Guan-Sheng Kim, Seongjin Moayeri, Mahtab Thai, April Cregar-Hernandez, Lynne McKasson, Linda Leppla, Stephen H. Johnson, Alan T.
Copyright Year	2017
Description	Journal: Bioorganic & medicinal chemistry letters Anthrax is a highly lethal disease caused by the Gram-(+) bacteria Bacillus anthracis. Edema toxin (ET) is a major contributor to the pathogenesis of disease in humans exposed to B. anthracis. ET is a bipartite toxin composed of two proteins secreted by the vegetative bacteria, edema factor (EF) and protective antigen (PA). Our work towards identifying a small molecule inhibitor of anthrax edema factor is the subject of this letter. First we demonstrate that the small molecule probe 5′-Fluorosulfonylbenzoyl 5′-adenosine (FSBA) reacts irreversibly with EF and blocks enzymatic activity. We then show that the adenosine portion of FSBA can be replaced to provide more drug-like molecules which are up to 1000-fold more potent against EF relative to FSBA, display low cross reactivity when tested against a panel of kinases, and are nanomolar inhibitors of EF in a cell-based assay of cAMP production.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875723/pdf
Ending Page	139
Page Count	6
Starting Page	134
ISSN	0960894X
DOI	10.1016/j.bmcl.2017.11.040
Journal	Bioorganic & medicinal chemistry letters
Issue Number	2
Volume Number	28
Language	English
Publisher	Elsevier BV
Publisher Date	2017-11-24
Access Restriction	Open
Subject Keyword	Journal: Bioorganic & medicinal chemistry letters Biochemistry and Molecular Biology Edema Factor Covalent Inhibitor
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Drug Discovery Biochemistry Molecular Biology Clinical Biochemistry Molecular Medicine Pharmaceutical Science