Towards selective inhibitors of adenylyl cyclase toxin from Bordetella pertussis

Trends in Microbiology
Roland Seifert, Stefan Dove

Abstract

Whooping cough is a very important medical problem that requires novel approaches for treatment. The disease is caused by Bordetella pertussis, with the calmodulin (CaM)-activated adenylyl cyclase (AC) toxin (also known as CyaA) being a major virulence factor. Hence, CyaA inhibitors could constitute novel therapeutics, but it has been difficult to develop potent drugs with high selectivity over mammalian membranous ACs (mACs). Recent studies have shown that bis-anthraniloyl-substituted nucleoside 5'-triphosphates are potent and selective CyaA inhibitors. In addition, the interaction of CyaA with CaM is very different from the interaction of membranous mAC1 with CaM. Accordingly, compounds that interfere with the CyaA-CaM interaction may constitute a novel class of drugs against whooping cough.

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Citations

Jul 16, 2013·Pharmacology & Therapeutics·Roland Seifert, Stefan Dove
Jul 16, 2014·Naunyn-Schmiedeberg's Archives of Pharmacology·Roland Seifert
Dec 22, 2014·Pharmacology & Therapeutics·Roland SeifertHeike Bähre
Jun 28, 2014·Biochemical and Biophysical Research Communications·Urike BeckertRoland Seifert
Jun 8, 2014·The Journal of Biological Chemistry·Edithe SelwaThérèse E Malliavin
Jun 9, 2021·European Journal of Medicinal Chemistry·Petra BřehováZlatko Janeba

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