Arsenault, J, Ferrari, E, Niranjan, D et al. (5 more authors) (2013) Stapling of the botulinum type A protease to growth factors and neuropeptides allows selective targeting of neuroendocrine cells. Journal Of Neurochemistry, 126 (2). 223 - 233. ISSN 1471-4159
Abstract
Precise cellular targeting of macromolecular cargos has important biotechnological and medical implications. Using a recently established ‘protein stapling’ method, we linked the proteolytic domain of botulinum neurotoxin type A (BoNT/A) to a selection of ligands to target neuroendocrine tumor cells. The botulinum proteolytic domain was chosen because of its well-known potency to block the release of neurotransmitters and hormones. Among nine tested stapled ligands, the epidermal growth factor was able to deliver the botulinum enzyme into pheochromocytoma PC12 and insulinoma Min6 cells; ciliary neurotrophic factor was effective on neuroblastoma SH-SY5Y and Neuro2A cells, whereas corticotropin-releasing hormone was active on pituitary AtT- 20 cells and the two neuroblastoma cell lines. In neuronal cultures, the epidermal growth factor- and ciliary neurotrophic factor-directed botulinum enzyme targeted distinct subsets of neurons whereas the whole native neurotoxin targeted the cortical neurons indiscriminately. At nanomolar concentrations, the retargeted botulinum molecules were able to inhibit stimulated release of hormones from tested cell lines suggesting their application for treatments of neuroendocrine disorders.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2013 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited |
Keywords: | botulinum, growth factor, neuroendocrine tumor, neuropeptide, SNAP25, targeting |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Funding Information: | Funder Grant number MRC U10578791 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 28 Apr 2014 13:27 |
Last Modified: | 28 Apr 2014 13:27 |
Published Version: | http://dx.doi.org/10.1111/jnc.12284 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1111/jnc.12284 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:78733 |