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Multivalent Inhibitors of Channel-Forming Bacterial Toxins

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Uptake and Trafficking of Protein Toxins

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 406))

Abstract

Rational design of multivalent molecules represents a remarkable modern tool to transform weak non-covalent interactions into strong binding by creating multiple finely-tuned points of contact between multivalent ligands and their supposed multivalent targets. Here, we describe several prominent examples where the multivalent blockers were investigated for their ability to directly obstruct oligomeric channel-forming bacterial exotoxins, such as the pore-forming bacterial toxins and B component of the binary bacterial toxins. We address problems related to the blocker/target symmetry match and nature of the functional groups, as well as chemistry and length of the linkers connecting the functional groups to their multivalent scaffolds. Using the anthrax toxin and AB5 toxin case studies, we briefly review how the oligomeric toxin components can be successfully disabled by the multivalent non-channel-blocking inhibitors, which are based on a variety of multivalent scaffolds.

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Acknowledgements

Our laboratory research is supported by the startup funds from The Catholic University of America and by NIAID of the NIH under award number 1R15AI099897-01A1.

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  1. Department of Biology, The Catholic University of America, Washington, D.C., 20064, USA

    Goli Yamini & Ekaterina M. Nestorovich

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  1. Goli Yamini
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  2. Ekaterina M. Nestorovich
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Correspondence to Ekaterina M. Nestorovich .

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  1. Institute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany

    Holger Barth

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Yamini, G., Nestorovich, E.M. (2016). Multivalent Inhibitors of Channel-Forming Bacterial Toxins. In: Barth, H. (eds) Uptake and Trafficking of Protein Toxins. Current Topics in Microbiology and Immunology, vol 406. Springer, Cham. https://doi.org/10.1007/82_2016_20

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