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!
Make way for the mini flying machines
21.03.2018 | American Chemical Society
New 4-D printer could reshape the world we live in
21.03.2018 | American Chemical Society
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.
In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...
Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...
19.03.2018 | Event News
16.03.2018 | Event News
13.03.2018 | Event News
21.03.2018 | Physics and Astronomy
21.03.2018 | Materials Sciences
21.03.2018 | Life Sciences