A Supramolecular Approach toward Bioinspired PAMAM-Dendronized Fusion Toxins

Macromolecular Bioscience
Seah Ling KuanTanja Weil

Abstract

Nature has provided a highly optimized toolbox in bacterial endotoxins with precise functions dictated by their clear structural division. Inspired by this streamlined design, a supramolecular approach capitalizing on the strong biomolecular (streptavidin (SA))-biotin interactions is reported herein to prepare two multipartite fusion constructs, which involves the generation 2.0 (D2) or generation 3.0 (D3) polyamidoamine-dendronized transporter proteins (dendronized streptavidin (D3SA) and dendronized human serum albumin (D2HSA)) non-covalently fused to the C3bot1 enzyme from Clostridium botulinum, a potent and specific Rho-inhibitor. The fusion constructs, D3SA-C3 and D2HSA-C3, represent the first examples of dendronized protein transporters that are fused to the C3 enzyme, and it is successfully demonstrated that the C3 Rho-inhibitor is delivered into the cytosol of mammalian cells as determined from the characteristic C3-mediated changes in cell morphology and confocal microscopy. The design circumvents the low uptake of the C3 enzyme by eukaryotic cells and holds great promise for reprogramming the properties of toxin enzymes using a supramolecular approach to broaden their therapeutic applications.

References

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Oct 30, 2012·Organic & Biomolecular Chemistry·Yutaro MoriNoriho Kamiya
Dec 6, 2012·Biomacromolecules·Seah Ling KuanTanja Weil
Oct 26, 2013·Journal of the American Chemical Society·Seah Ling KuanTanja Weil
Jan 1, 2014·Angewandte Chemie·David Y W NgTanja Weil
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Jul 16, 2015·Frontiers in Immunology·Holger BarthChristina Förtsch

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Citations

Nov 20, 2018·Chemical Society Reviews·Seah Ling KuanTanja Weil
Jul 19, 2019·Advanced Healthcare Materials·Astrid Johanna HeckHolger Barth
Aug 22, 2018·Advanced Science·Seah Ling KuanTanja Weil

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Botulism (ASM)

Botulism is a rare but serious paralytic illness caused by a nerve toxin that is produced by the bacterium clostridium botulinum. Discover the latest research on botulism here.

Botulism

Botulism is a rare but serious paralytic illness caused by a nerve toxin that is produced by the bacterium clostridium botulinum. Discover the latest research on botulism here.

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