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Here we identified poly(amido amine) (PAMAM) dendrimers as novel blockers for the pore-forming B components of the binary anthrax toxin (PA63) and Clostridium botulinum C2 toxin (C2IIa). These pores are essential for delivery of the enzymatic A components of the internalized toxins from endosomes into the cytosol of target cells. We demonstrate that at low \u03bcM concentrations cationic PAMAM dendrimers block PA63 and C2IIa to inhibit channel-mediated transport of the A components, thereby protecting HeLa and Vero cells from intoxication. By channel reconstitution and high-resolution current recording, we show that the PAMAM dendrimers obstruct transmembrane PA63 and C2IIa pores in planar lipid bilayers at nM concentrations. These findings suggest a new potential role for the PAMAM dendrimers as effective polyvalent channel-blocking inhibitors, which can protect human target cells from intoxication with binary toxins from pathogenic bacteria.<\/jats:p>","DOI":"10.1021\/bm500328v","type":"journal-article","created":{"date-parts":[[2014,6,23]],"date-time":"2014-06-23T07:21:03Z","timestamp":1403508063000},"page":"2461-2474","source":"Crossref","is-referenced-by-count":24,"title":["Cationic PAMAM Dendrimers as Pore-Blocking Binary\nToxin Inhibitors"],"prefix":"10.1021","volume":"15","author":[{"given":"Philip","family":"Fo\u0308rstner","sequence":"first","affiliation":[{"name":"University of Ulm Medical Center , , ,","place":["Ulm, Germany, D-89081"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabienne","family":"Bayer","sequence":"additional","affiliation":[{"name":"University of Ulm Medical Center , , ,","place":["Ulm, Germany, D-89081"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nnanya","family":"Kalu","sequence":"additional","affiliation":[{"name":"The Catholic University of America , , , ,","place":["Washington, D.C., United States, 20064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Felsen","sequence":"additional","affiliation":[{"name":"University of Ulm Medical Center , , ,","place":["Ulm, Germany, D-89081"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Fo\u0308rtsch","sequence":"additional","affiliation":[{"name":"University of Ulm Medical Center , , ,","place":["Ulm, Germany, D-89081"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abrar","family":"Aloufi","sequence":"additional","affiliation":[{"name":"The Catholic University of America , , , ,","place":["Washington, D.C., United States, 20064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Y. 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