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UW-Madison Scientists Zero In On Drugs' Sweet Spots

Date:
August 12, 2005
Source:
University of Wisconsin-Madison
Summary:
Employing a simple new technique to manipulate the sugars that power many front-line drugs, a team of Wisconsin scientists has enhanced the antic-cancer properties of a digitalis, a drug commonly used to treat heart disease.

MADISON -- Employing a simple new technique to manipulate the sugarsthat power many front-line drugs, a team of Wisconsin scientists hasenhanced the antic-cancer properties of a digitalis, a drug commonlyused to treat heart disease.

Reporting the work in the Aug. 8 edition of the Proceedings of theNational Academy of Sciences, a team led by University ofWisconsin-Madison professor of pharmaceutical sciences Jon S. Thorson,describes a series of experiments that boosted the cell-killing potencyand tumor specificity of the drug, derived from the foxglove plant andused to stimulate the heart. The drug is suspected to have anti-cancerproperties, but its use to treat cancer has been little explored.

The new work is important because it provides scientists anddrug companies with a quick and easy way to manipulate the sugars foundin chemicals produced in nature. Such chemicals -- often found inmicrobes, plants and marine organisms -- are the bedrock agents uponwhich many leading drugs are built. The ways sugar groups are organizedon a molecule often dictate the agent's biological effects.

"In the past, to alter the sugars attached to these drugs wasvery difficult," explains Thorson, of the UW-Madison Pharmacy School'sLaboratory for Biosynthetic Chemistry. "These are very complexmolecules."

The new technique replaces enzymes, biological catalysts, witha robust chemical method, allowing researchers to easily manipulate andexchange the sugars found in natural agents.

Critically, the method allows medicinal chemists to investigatethe biological effects of the many forms of sugars or carbohydratesfound in nature. "There are many different variations of sugars --they're all over the place in nature -- and they are very important.This method allows us to rapidly scan the roles of these sugars incomplex natural products."

The simplification of the process to manipulate natural sugarscould help make natural products more appealing to the pharmaceuticalindustry. Despite the fact that 60-75 percent of drugs approved totreat infectious disease and cancer over the past 25 years are ofnatural origin, many companies have lost interest in developing naturalproducts because of the complex chemistry that underpins them.

The ability to zero in on the sweet spot of drugs derived fromnatural products promises to help scientists specify the role of thesugar and make new drugs or enhance old ones to greater precision andeffect. The series of experiments performed by Thorson's team, forexample, may help researchers enhance the anti-cancer effects ofdigitalis and downshift its influence on the heart, thus avoidingpotential detrimental effects in cancer patients.

"I think this (technique) is going to send us down someinteresting mechanistic roads," Thorson notes. "Digitalis hasn't beenaggressively pursued as an anti-cancer agent."

According to Thorson, the technology can be widely applied:"We've already taken this chemistry and applied it to many differentdrug 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 isthe best way to do it."

The new technique, according to Thorson, will play a prominentrole in the new UW-Madison National Cooperative Drug Discovery Group, aconsortium of UW-Madison scientists seeking to develop new anti-cancerdrugs from natural products. The group was recently formed with thehelp of a $5.6 million grant from the National Cancer Institute (NCI).

The new work by Thorson was supported by the NationalInstitutes of Health and the NCI. Thorson's collaborators includeJoseph Langenhan, a former UW-Madison graduate student andpost-doctoral fellow and now a chemistry professor at SeattleUniversity; Noel R. Peters, and Professor F. Michael Hoffmann of theUW-Madison Comprehensive Cancer Center's Small Molecule ScreeningFacility; and Ilia A. Guzei, director of crystallography in theUW-Madison department of chemistry.



Story Source:

The above story is based on materials provided by University of Wisconsin-Madison. Note: Materials may be edited for content and length.


Cite This Page:

University of Wisconsin-Madison. "UW-Madison Scientists Zero In On Drugs' Sweet Spots." ScienceDaily. ScienceDaily, 12 August 2005. <www.sciencedaily.com/releases/2005/08/050811105643.htm>.
University of Wisconsin-Madison. (2005, August 12). UW-Madison Scientists Zero In On Drugs' Sweet Spots. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2005/08/050811105643.htm
University of Wisconsin-Madison. "UW-Madison Scientists Zero In On Drugs' Sweet Spots." ScienceDaily. www.sciencedaily.com/releases/2005/08/050811105643.htm (accessed July 31, 2014).

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