Issue 26, 2013
From the journal:

Organic & Biomolecular Chemistry

Picomolar inhibition of cholera toxin by a pentavalent ganglioside GM1os-calix[5]arene†

Jaime Garcia-Hartjes,‡a   Silvia Bernardi,‡b   Carel A. G. M. Weijers,a   Tom Wennekes,a   Michel Gilbert,c   Francesco Sansone,b   Alessandro Casnati*b  and  Han Zuilhof*ad  

* Corresponding authors

a Laboratory of Organic Chemistry, Wageningen University, Dreijenplein 8, 6703 HB Wageningen, The Netherlands
E-mail: Han.Zuilhof@wur.nl

b Università degli Studi di Parma, Dipartimento di Chimica, Parco Area delle Scienze 17/a, 43124 Parma, Italy
E-mail: Casnati@unipr.it

c Institute for Biological Sciences, National Research Council Canada, 100 Sussex Drive, Ottawa, Ontario, Canada

d Department of Chemical and Materials Engineering, King Abdulaziz University, Jeddah, Saudi Arabia

Abstract

Cholera toxin (CT), the causative agent of cholera, displays a pentavalent binding domain that targets the oligosaccharide of ganglioside GM1 (GM1os) on the periphery of human abdominal epithelial cells. Here, we report the first GM1os-based CT inhibitor that matches the valency of the CT binding domain (CTB). This pentavalent inhibitor contains five GM1os moieties linked to a calix[5]arene scaffold. When evaluated by an inhibition assay, it achieved a picomolar inhibition potency (IC50 = 450 pM) for CTB. This represents a significant multivalency effect, with a relative inhibitory potency of 100 000 compared to a monovalent GM1os derivative, making GM1os-calix[5]arene one of the most potent known CTB inhibitors.

Graphical abstract: Picomolar inhibition of cholera toxin by a pentavalent ganglioside GM1os-calix[5]arene

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Article information

DOI
https://doi.org/10.1039/C3OB40515J
Article type
Paper
Submitted
13 Mar 2013
Accepted
29 Apr 2013
First published
20 May 2013
This article is Open Access
Creative Commons BY license

Org. Biomol. Chem., 2013,11, 4340-4349

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Picomolar inhibition of cholera toxin by a pentavalent ganglioside GM1os-calix[5]arene

J. Garcia-Hartjes, S. Bernardi, C. A. G. M. Weijers, T. Wennekes, M. Gilbert, F. Sansone, A. Casnati and H. Zuilhof, Org. Biomol. Chem., 2013, 11, 4340 DOI: 10.1039/C3OB40515J

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