Title |
A Protein‐Based Pentavalent Inhibitor of the Cholera Toxin B‐Subunit
|
---|---|
Published in |
Angewandte Chemie. International Edition, July 2014
|
DOI | 10.1002/anie.201404397 |
Pubmed ID | |
Authors |
Thomas R. Branson, Tom E. McAllister, Jaime Garcia‐Hartjes, Martin A. Fascione, James F. Ross, Stuart L. Warriner, Tom Wennekes, Han Zuilhof, W. Bruce Turnbull |
Abstract |
Protein toxins produced by bacteria are the cause of many life-threatening diarrheal diseases. Many of these toxins, including cholera toxin (CT), enter the cell by first binding to glycolipids in the cell membrane. Inhibiting these multivalent protein/carbohydrate interactions would prevent the toxin from entering cells and causing diarrhea. Here we demonstrate that the site-specific modification of a protein scaffold, which is perfectly matched in both size and valency to the target toxin, provides a convenient route to an effective multivalent inhibitor. The resulting pentavalent neoglycoprotein displays an inhibition potency (IC50) of 104 pM for the CT B-subunit (CTB), which is the most potent pentavalent inhibitor for this target reported thus far. Complexation of the inhibitor and CTB resulted in a protein heterodimer. This inhibition strategy can potentially be applied to many multivalent receptors and also opens up new possibilities for protein assembly strategies. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 4 | 31% |
South Africa | 1 | 8% |
Netherlands | 1 | 8% |
Unknown | 7 | 54% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 8 | 62% |
Scientists | 5 | 38% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Japan | 1 | 1% |
Netherlands | 1 | 1% |
China | 1 | 1% |
France | 1 | 1% |
Unknown | 71 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 21 | 28% |
Researcher | 14 | 19% |
Student > Master | 9 | 12% |
Student > Bachelor | 6 | 8% |
Professor > Associate Professor | 6 | 8% |
Other | 8 | 11% |
Unknown | 11 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Chemistry | 39 | 52% |
Biochemistry, Genetics and Molecular Biology | 10 | 13% |
Agricultural and Biological Sciences | 9 | 12% |
Medicine and Dentistry | 2 | 3% |
Earth and Planetary Sciences | 1 | 1% |
Other | 3 | 4% |
Unknown | 11 | 15% |