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Small molecule inhibitors of Clostridium difficile toxin B-induced cellular damage.

Chem. Biol.. 2015-02; 
TamJohn,BeilhartzGreg L,AugerAnick,GuptaPulkit,TherienAlex G,MelnykRom
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Custom Vector Construction … changed to AAAA (Alanine) respectively and inserted into pMal-c5E vector The mutant sequences were obtained from Genscript in aliquots of 4uLs These were the following sequences of mutants obtained ZF-1 Mutant of CPSF30 … Get A Quote

摘要

Clostridium difficile causes life-threatening diarrhea through the actions of its homologous toxins TcdA and TcdB on human colonocytes. Therapeutic agents that block toxin-induced damage are urgently needed to prevent the harmful consequences of toxin action that are not addressed with current antibiotic-based treatments. Here, we developed an imaging-based phenotypic screen to identify small molecules that protected human cells from TcdB-induced cell rounding. A series of structurally diverse compounds with antitoxin activity were identified and found to act through one of a small subset of mechanisms, including direct binding and sequestration of TcdB, inhibition of endosomal maturation, and noncompet... More

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