title: Towards selective inhibitors of adenylyl cyclase toxin from Bordetella pertussis.
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.
authors.affiliation: Institute of Pharmacology, Medical School of Hannover, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Seifert
authors.forename: Stefan
authors.initials: S
authors.lastname: Dove
mesh_terms: D037361:Adenylate Cyclase Toxin / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001886:Bordetella pertussis / Q000187:drug effects* / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D012265:Ribonucleotides / Q000737:chemistry / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D012265:Ribonucleotides