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 Brought to light – chromobodies reveal changes in endogenous protein concentration in living cells
21.09.2018 | NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen

nachricht A one-way street for salt
21.09.2018 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Scientists present new observations to understand the phase transition in quantum chromodynamics

The building blocks of matter in our universe were formed in the first 10 microseconds of its existence, according to the currently accepted scientific picture. After the Big Bang about 13.7 billion years ago, matter consisted mainly of quarks and gluons, two types of elementary particles whose interactions are governed by quantum chromodynamics (QCD), the theory of strong interaction. In the early universe, these particles moved (nearly) freely in a quark-gluon plasma.

This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.

Then, in a phase transition, they combined and formed hadrons, among them the building blocks of atomic nuclei, protons and neutrons. In the current issue of...

Im Focus: Patented nanostructure for solar cells: Rough optics, smooth surface

Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.

"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...

Im Focus: New soft coral species discovered in Panama

A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.

Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...

Im Focus: New devices based on rust could reduce excess heat in computers

Physicists explore long-distance information transmission in antiferromagnetic iron oxide

Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.

Im Focus: Finding Nemo's genes

An international team of researchers has mapped Nemo's genome

An international team of researchers has mapped Nemo's genome, providing the research community with an invaluable resource to decode the response of fish to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

"Boston calling": TU Berlin and the Weizenbaum Institute organize a conference in USA

21.09.2018 | Event News

One of the world’s most prominent strategic forums for global health held in Berlin in October 2018

03.09.2018 | Event News

4th Intelligent Materials - European Symposium on Intelligent Materials

27.08.2018 | Event News

 
Latest News

Three NASA missions return first-light data

24.09.2018 | Physics and Astronomy

Brown researchers teach computers to see optical illusions

24.09.2018 | Information Technology

Astrophysicists measure precise rotation pattern of sun-like stars for the first time

21.09.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>