Nanomolar cholera toxin inhibitors based on symmetrical pentavalent ganglioside GM1os-sym-corannulenes

Martin Mattarella; Jaime Garcia-Hartjes; Tom Wennekes; Han Zuilhof; Jay S Siegel

doi:10.1039/c3ob40438b

Nanomolar cholera toxin inhibitors based on symmetrical pentavalent ganglioside GM1os-sym-corannulenes

Org Biomol Chem. 2013 Jul 14;11(26):4333-4339. doi: 10.1039/c3ob40438b. Epub 2013 Jun 4.

Authors

Martin Mattarella¹, Jaime Garcia-Hartjes², Tom Wennekes², Han Zuilhof³, Jay S Siegel¹

Affiliations

¹ Institute of Organic Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. jss@oci.uzh.ch.
² Laboratory of Organic Chemistry, Wageningen University, Dreijenplein 8, 6703 HB, Wageningen, The Netherlands.
³ Laboratory of Organic Chemistry, Wageningen University, Dreijenplein 8, 6703 HB, Wageningen, The Netherlands and Department of Chemical and Materials Engineering, King Abdulaziz University, Jeddah, Saudi Arabia. han.zuilhof@wur.nl.

PMID: 23736158
DOI: 10.1039/c3ob40438b

Abstract

Eight symmetric and pentavalent corannulene derivatives were functionalized with galactose and the ganglioside GM1-oligosaccharide (GM1os) via copper-catalyzed alkyne-azide cycloaddition (CuAAC) reactions. The compounds were evaluated for their ability to inhibit the binding of the pentavalent cholera toxin to its natural ligand, ganglioside GM1. In this assay, all ganglioside GM1os-sym-corannulenes proved to be highly potent nanomolar inhibitors of cholera toxin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antitoxins / chemistry*
Antitoxins / pharmacology
Cholera Toxin / antagonists & inhibitors*
Cholera Toxin / metabolism
G(M1) Ganglioside / analogs & derivatives*
G(M1) Ganglioside / metabolism
G(M1) Ganglioside / pharmacology
Galactose / chemistry*
Galactose / pharmacology
Polycyclic Aromatic Hydrocarbons / chemistry*
Polycyclic Aromatic Hydrocarbons / pharmacology

Substances

Antitoxins
Polycyclic Aromatic Hydrocarbons
corannulene
G(M1) Ganglioside
Cholera Toxin
Galactose