Sweet success in drug sugar studies
that power many front-line drugs, which has resulted in the
enhancement of a drug for heart disease. Manipulating the natural
sugars in a drug could help make natural products more appealing to
the pharmaceutical industry.
The ways sugar groups are organised on a molecule often dictate the agent's biological effects. This latest research provides scientists and drug companies with a quick and easy way to manipulate the sugars found in chemicals produced in nature.
The new technique replaces enzymes, biological catalysts, with a robust chemical method, allowing researchers to easily manipulate and exchange the sugars found in natural agents. Such chemicals - often found in microbes, plants and marine organisms - are the foundation upon which many leading drugs are built.
University of Wisconsin-Madison scientists describe a series of experiments that boosted the cell-killing potency and tumour specificity of digitalis, derived from the foxglove plant and used to stimulate the heart.
The drug is suspected to have anti-cancer properties, but its use to treat cancer has been rarely explored.
"In the past, to alter the sugars attached to these drugs was very difficult," explained Jon Thorson, professor of pharmaceutical sciences, at UW-Madison University.
Despite the fact that 60-75 per cent of drugs approved to treat infectious disease and cancer over the past 25 years are of natural origin, many companies have lost interest in developing natural products because of the complex chemistry that characterises them.
The ability to zero in on the sweet spot of drugs derived from natural products promises to help scientists specify the role of the sugar and make new drugs or enhance old ones to greater precision and effect.
"This method allows us to rapidly scan the roles of these sugars in complex natural products. There are many different variations of sugars, they're all over the place in nature and they are very important," Thorson commented.
According to Thorson, the technology can be widely applied to many different drug classes.
"It's possible to extend it to antibiotics and antivirals. If you want to plug in a sugar and see what it does for you, this is the best way to do it," he said.
The new technique will play a prominent role in the new UW-Madison National Cooperative Drug Discovery Group, a consortium of UW-Madison scientists seeking to develop new anti-cancer drugs from natural products. The group was recently formed with the help of a $5.6 million (€4.5 million) grant from the National Cancer Institute (NCI).
The research appears in the Aug. 8 edition of the Proceedings of the National Academy of Sciences.
