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 'Y' a protein unicorn might matter in glaucoma
23.10.2017 | Georgia Institute of Technology

nachricht Microfluidics probe 'cholesterol' of the oil industry
23.10.2017 | Rice University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Salmonella as a tumour medication

HZI researchers developed a bacterial strain that can be used in cancer therapy

Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Symposium on Driving Simulation

23.10.2017 | Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

 
Latest News

Microfluidics probe 'cholesterol' of the oil industry

23.10.2017 | Life Sciences

Gamma rays will reach beyond the limits of light

23.10.2017 | Physics and Astronomy

The end of pneumonia? New vaccine offers hope

23.10.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>