A Protein‐Based Pentavalent Inhibitor of the Cholera Toxin B‐Subunit1. Issue 32 (2nd July 2014)

• Record Type: Journal Article
• Authors: Branson, Thomas R.; McAllister, Tom E.; Garcia‐Hartjes, Jaime; Fascione, Martin A.; Ross, James F.; Warriner, Stuart L.; Wennekes, Tom; Zuilhof, Han; Turnbull, W. Bruce
• Is Part Of: Angewandte Chemie international edition. Volume 53:Issue 32(2014)
• Page Start: 8323
• Page End: 8327
• Publication Date: 2014-07-02
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201404397
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 p<sc>M</sc> 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.</p> </abstract>