Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cholera: Fighting Fire with Fire

04.07.2014

 

Binding at five sites: effective cholera inhibitor based on cholera toxins

 

Cholera against cholera: a novel inhibitor prevents the cholera toxin from binding to carbohydrates found on the surface of intestinal cells. An international team of researchers has described their elegant concept in the journal Angewandte Chemie:

The protein scaffold of the inhibitor is based on an inactive cholera toxin. It is equipped with five sugar moieties to act as ligands. The inhibitor’s size and number of binding sites are both perfectly matched to the cholera toxin bearing five binding sites.

Cholera is a bacterial infectious disease that is primarily transmitted through insufficiently treated drinking water and contaminated foods. The actual pathogen is a toxin released by the bacteria; it attacks the cells of the intestine and causes life-threatening diarrhea.

... more about:
»Cholera »Fighting »GM1 »ligands »sugar

Cholera toxin is a protein consisting of a toxic A unit and five nontoxic B units (CTB). Its shape resembles a blossom with five petals. The “petals” are nontoxic, but they bind to special carbohydrates—the oligosaccharide units on glycolipid GM1—on the surface of intestinal cells, initiating uptake of the toxin. Each of the five B subunits possesses a specific binding site for the special sugar motif.

In order to put a stop to the pentavalent cholera toxin, scientist at the University of Leeds (UK), Wageningen University (Netherlands), and King Abdulaziz University in Jeddah (Saudi Arabia) have now developed a pentavalent inhibitor. To make it properly fit with its counterpart they fell back on the old principle of “fighting fire with fire”: They used an inactive version of the five “petals” from CTB subunits as the protein scaffold for their inhibitor.

Led by Bruce Turnbull, the researchers induced a mutation in the GM1 binding site of the CTB subunits so that the inhibitor does not bind to the intestinal cells. In addition, a special side chain on each of the “petals” was chemically altered so that they could undergo a coupling reaction by which five ligands were then attached with flexible spacers. The ligands were chosen to be the ideal binding partners for the toxin:

the saccharide units from glycolipid GM1. The advantage of this method is that the inhibitor presents the toxin with five ligands that are in exactly the same distance apart as the five binding sites of the toxin, making it the perfect counterpart. The potency of the new pentavalent inhibitor for its target molecule is thus correspondingly high.

Although the synthesis of the sugar motif is relatively complicated, the protein scaffold can easily be produced genetically on an industrial scale, and can easily be chemically modified and the saccharides attached. The researchers hope that this synthetic technique can be used to develop further multivalent inhibitors for other protein–carbohydrate interactions.

About the Author

Dr. Bruce Turnbull is an Associate Professor in the School of Chemistry and Astbury Centre for Structural Molecular Biology at the University of Leeds. He chairs an EU COST Action network on Multivalent Glycosystems for Nanoscience and was the 2013 recipient of the Royal Society of Chemistry Carbohydrate Award.

Author: W. Bruce Turnbull, University of Leeds (United Kingdom), http://www.chem.leeds.ac.uk/People/Turnbull.html

Title: A Protein-Based Pentavalent Inhibitor of the Cholera Toxin B-Subunit

Angewandte Chemie International Edition, Permalink to the article: http://dx.doi.org/10.1002/anie.201404397

W. Bruce Turnbull | GDCh

Further reports about: Cholera Fighting GM1 ligands sugar

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>