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 Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

nachricht The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

IHP presents the fastest silicon-based transistor in the world

05.12.2016 | Power and Electrical Engineering

InLight study: insights into chemical processes using light

05.12.2016 | Materials Sciences

High-precision magnetic field sensing

05.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>