Synthesis and cholera toxin binding properties of multivalent GM1 mimics

• Published in: Organic & biomolecular chemistry Vol. 2; no. 14; p. 2113
• Main Authors: Arosio, Daniela, Vrasidas, Ioannis, Valentini, Paola, Liskamp, Rob M J, Pieters, Roland J, Bernardi, Anna
• Format: Journal Article
• Language: English
• Published: England 21-07-2004
• Subjects: Benzoates - chemical synthesis; Benzoates - chemistry; Carbohydrate Sequence; Cholera Toxin - antagonists & inhibitors; Cholera Toxin - chemistry; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside - chemical synthesis; G(M1) Ganglioside - chemistry; Ligands; Molecular Mimicry; Molecular Sequence Data; Molecular Structure; Surface Plasmon Resonance - methods
• ISSN: 1477-0520
• DOI: 10.1039/b405344c

Dendrimers based on the 3,5-di-(2-aminoethoxy)-benzoic acid branching unit were used to attach multiple copies of a GM1 mimic for inhibition of cholera toxin binding. Systems up to octavalent were synthesized along with relevant reference compounds that contained in one case the ligand in a monovalent format and in another case the scaffold but not the ligand. Using a surface plasmon resonance inhibition assay the prepared inhibitors showed good inhibition. While the monovalent GM1 mimic showed the expected inhibition in the 200 microM range the multivalent scaffolds led to increased binding. The tetravalent compound was shown to be 440-fold more potent than its monovalent counterpart. The octavalent analog, however, was the most potent compound as determined using an ELISA assay.