Fucose-Galactose Polymers Inhibit Cholera Toxin Binding to Fucosylated Structures and Galactose-Dependent Intoxication of Human Enteroids.

ACS Infectious Diseases
Jakob CervinUlf Yrlid

Abstract

A promising strategy to limit cholera severity involves blockers mimicking the canonical cholera toxin ligand (CT) ganglioside GM1. However, to date the efficacies of most of these blockers have been evaluated in noncellular systems that lack ligands other than GM1. Importantly, the CT B subunit (CTB) has a noncanonical site that binds fucosylated structures, which in contrast to GM1 are highly expressed in the human intestine. Here we evaluate the capacity of norbornene polymers displaying galactose and/or fucose to block CTB binding to immobilized protein-linked glycan structures and also to primary human and murine small intestine epithelial cells (SI ECs). We show that the binding of CTB to human SI ECs is largely dependent on the noncanonical binding site, and interference with the canonical site has a limited effect while the opposite is observed with murine SI ECs. The galactose-fucose polymer blocks binding to fucosylated glycans but not to GM1. However, the preincubation of CT with the galactose-fucose polymer only partially blocks toxic effects on cultured human enteroid cells, while preincubation with GM1 completely blocks CT-mediated secretion. Our results support a model whereby the binding of fucose to the noncano...Continue Reading

References

Jul 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·J HolmgrenL Svennerholm
Jan 1, 1973·Scandinavian Journal of Infectious Diseases·J HolmgrenL Svennerholm
Jan 1, 1970·The Journal of Clinical Investigation·J G BanwellA Mondal
May 1, 1968·The Journal of Clinical Investigation·C C CarpenterR W Steenberg
Dec 1, 1968·The Journal of Clinical Investigation·C C Carpenter, W B Greenough
Apr 1, 1995·Current Opinion in Structural Biology·E A Merritt, W G Hol
Feb 1, 1994·Protein Science : a Publication of the Protein Society·E A MerrittW G Hol
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·K TakamiyaS Aizawa
Jun 23, 1999·Proceedings of the National Academy of Sciences of the United States of America·K A SheikhR L Schnaar
Jul 16, 2004·Organic & Biomolecular Chemistry·Daniela ArosioAnna Bernardi
Mar 27, 2007·The Journal of Biological Chemistry·Kengo MatsumuraNaoyuki Taniguchi
Jul 13, 2007·Chembiochem : a European Journal of Chemical Biology·Aliaksei V PukinRoland J Pieters
Dec 1, 2007·Chemical Communications : Chem Comm·Hilbert M BranderhorstRoland J Pieters
Feb 7, 2012·Biochemical and Biophysical Research Communications·Julie E HeggelundUte Krengel
Jan 27, 2015·Annual Review of Pathology·Sean R StowellRichard D Cummings
Jun 5, 2015·PLoS Neglected Tropical Diseases·Mohammad AliDavid A Sack
Aug 25, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Pawin PongkorpsakolChatchai Muanprasat
Apr 16, 2016·PLoS Pathogens·Julie Elisabeth HeggelundUte Krengel
May 11, 2016·The American Journal of Tropical Medicine and Hygiene·F Matthew KuhlmannJames M Fleckenstein
Jun 28, 2016·Journal of Medicinal Chemistry·Domenique D Zomer-van OmmenRoland J Pieters
Mar 18, 2017·Lancet·John D ClemensJan Holmgren
Aug 23, 2017·The Lancet Global Health·Jonathan KennedyDavid McCoy
Feb 9, 2018·Oncotarget·Ninon VeryIkram El Yazidi-Belkoura
Feb 13, 2018·PLoS Pathogens·Jakob CervinUlf Yrlid
Feb 23, 2018·PLoS Neglected Tropical Diseases·Soumita DasLars Eckmann
Mar 10, 2018·Beilstein Journal of Organic Chemistry·Vajinder Kumar, W Bruce Turnbull
Jan 11, 2019·Bioconjugate Chemistry·Diksha HaksarRoland J Pieters
Feb 6, 2019·Scientific Reports·Stanislas RebaudetRenaud Piarroux
Mar 3, 2019·Glycobiology·Hyun-Kyu ChoiHung-Jen Wu
Mar 8, 2019·Interface Focus·Anirudh SethiJennifer J Kohler

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
glycosylation
static light scattering
flow cytometry
light-scattering
gastric bypass
biopsies

Software Mentioned

GraphPad Prism
FlowJo
Prism

Related Concepts

Related Feeds

Addiction

This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.