Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Sweet insight: Discovery could speed drug development

23.08.2011
The surface of cells and many biologically active molecules are studded with sugar structures that are not used to store energy, but rather are involved in communication, immunity and inflammation.

In a similar manner, sugars attached to drugs can enhance, change or neutralize their effects, says Jon Thorson, a professor of pharmaceutical sciences at the University of Wisconsin-Madison School of Pharmacy.

Thorson, an expert in the attachment and function of these sugars, says that understanding and controlling them has major potential for improving drugs, but that researchers have been stymied because many novel sugars are difficult to create and manipulate. "The chemistry of these sugars is difficult, so we have been working on methods to make it more user friendly," he says.

Now, in a study published online in Nature Chemical Biology on Aug. 21, Thorson, graduate student Richard Gantt and postdoctoral fellow Pauline Peltier-Pain have described a simple process to separate the sugars from a carrier molecule, then attach them to a drug or other chemical. The process also causes a color change only among those molecules that have accepted the sugar. The change in color should support a screening system that would easily select out transformed molecules for further testing. "One can put 1,000 drug varieties on a plate and tell by color how many of them have received the added sugar," Thorson says.

Attached sugars play a key role in pharmacy, says Thorson. Not only can they change the solubility of a compound, but "there are transporters in the body that specifically recognize certain sugars, and pharmaceutical companies have taken advantage of this to direct molecules toward specific tissue or cell types. If we can build a toolbox that allows us to make these molecules on demand, we can ask, 'What will sugar A do when it's attached to drug B?'"

And although the new study was focused more on an improved technique rather than the alteration of drugs, Thorson adds that it does describe the production of some "really interesting sugar-appended drugs: anti-virals, antibiotics, anti-cancer and anti-inflammatory drugs. Follow-up studies are currently under way to explore the potential of these analogs."

The new molecules included 11 variants of vancomycin, a powerful antibiotic, each distinguished by the nature and number of attached sugars.

The essence of the new process is its starting point: a molecule that changes the energy dynamics of the sugar-attachment reaction, Thorson says. "This is one of the first systematic studies of the equilibrium of the reaction, and it shows we can drive it forward or in reverse, depending on the molecule that we start with."

In a single test tube, the new technique is able to detach the sugar from its carrier and reattach it to the biological target molecule, Thorson says. "Sugars are involved a vast range of biology, but there are still many aspects that are not well understood about the impact of attaching and removing sugars, partly because of the difficulty of analyzing and accessing these species."

Making variants of potential and existing drugs is a standard practice for drug-makers, and a recently published study by Peltier-Pain and Thorson revealed that attaching a certain sugar to the anti-coagulant Warfarin destroys its anti-clotting ability. The transformed molecule, however, "suddenly becomes quite cytotoxic — it kills cells," he says. "We don't know the mechanism, but there is some interest in using it to fight cancer because it seems to act specifically on certain cells."

Sugars are also attached to proteins, cell surfaces and many other locations in biology, Thorson says. "By simplifying the attachment, we are improving the pharmacologist's toolbox. This study provides access to new reagents and offers a very convenient screening for new catalysts and/or new drugs, and for other things we haven't yet thought of. We believe this is going to open up a lot of doors."

Jon S. Thorson | EurekAlert!
Further information:
http://www.wisc.edu

More articles from Life Sciences:

nachricht Scientists unlock ability to generate new sensory hair cells
22.02.2017 | Brigham and Women's Hospital

nachricht New insights into the information processing of motor neurons
22.02.2017 | Max Planck Florida Institute for Neuroscience

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>