100596-53-0Relevant academic research and scientific papers
NMR-based discovery of lead inhibitors that block DNA binding of the human papillomavirus E2 protein
Hajduk, Philip J.,Dinges, Jürgen,Miknis, Gregory F.,Merlock, Megan,Middleton, Tim,Kempf, Dale J.,Egan, David A.,Walter, Karl A.,Robins, Terry S.,Shuker, Suzy B.,Holzman, Thomas F.,Fesik, Stephen W.
, p. 3144 - 3150 (1997)
The E2 protein is required for the replication of human papillomaviruses (HPVs), which are responsible for anogenital warts and cervical carcinomas. Using an NMR-based screen we tested compounds for binding to the DNA-binding domain of the HPV-E2 protein. Three classes of compounds were identified which bound to two distinct sites on the protein. Biphenyl and biphenyl ether compounds containing a carboxylic acid bind to a site near the DNA recognition helix and inhibit the binding of E2 to DNA. Benzophenone- containing compounds which lack a carboxylic acid group bind to the β- barrel formed by the dimer interface and exhibit negligible effects on the binding of E2 to DNA. Structure-activity relationships from the biphenyl and biphenyl ether compounds were combined to produce a compound [5-(3'- (3'',5''-dichlorophenoxy)-phenyl)-2,4-pentadienoic acid] with an IC50 value of approximately 10 μM. This compound represents a useful lead for the development of antiviral agents that interfere with HPV replication and further illustrates the usefulness of the SAR by NMR method in the drug discovery process.
ANTI-BACTERIAL COMPOSITIONS AND METHODS INCLUDING TARGETING VIRULENCE FACTORS OF STAPHYLOCOCCUS AUREUS
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Page/Page column 26, (2012/02/03)
This disclosure relates to compositions and methods including for the inhibition, prevention, and/or treatment of microbial infections, including infections from such pathogens as Staphylococcus aureus.
Inhibition of staphyloxanthin virulence factor biosynthesis in Staphylococcus aureus: In vitro, in vivo, and crystallographic results
Song, Yongcheng,Liu, Chia-I.,Lin, Fu-Yang,Joo, Hwan No,Hensler, Mary,Liu, Yi-Liang,Jeng, Wen-Yih,Low, Jennifer,Liu, George Y.,Nizet, Victor,Wang, Andrew H.-J.,Oldfield, Eric
experimental part, p. 3869 - 3880 (2009/12/28)
The gold color of Staphylococcus aureus is derived from the carotenoid staphyloxanthin, a virulence factor for the organism. Here, we report the synthesis and activity of a broad variety of staphyloxanthin biosynthesis inhibitors that inhibit the first co
