Cell surfaces and many biologically active molecules are covered with sugar structures that are involved in communication, immunity, and inflammation. Likewise, sugars attached to drugs can enhance, change or neutralize the drug’s effects, says Jon Thorson, a professor of pharmaceutical sciences at the University of Wisconsin-Madison School of Pharmacy.
As an expert in the attachment and function of these sugars, Thorson says there is major potential for improving drugs simply by understanding and controlling the sugars.
In a study published online in the journal Nature Chemical Biology on August 21, 2011, Thorson, graduate student Richard Gantt, and postdoctoral fellow Pauline Peltier-Pain described how they separated sugars from a carrier molecule and then attached them to a drug or other chemical. During their research, they discovered a color change is caused by the process, but only among those molecules that have accepted the sugar. This change in color supports a screening system that would easily reveal altered molecules for further testing. “One can put 1000 drug varieties on a plate and tell by color how many of them have received the added sugar,” Thorson says.
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.
Creating variations of existing drugs is a common practice for pharmaceutical companies, and a recently published study by Peltier-Pain and Thorson revealed that attaching a certain sugar to the anticoagulant warfarin destroys its anticlotting capabilities. The altered molecule, however, “suddenly becomes quite cytotoxic – it kills cells,” according to Thorson. Furthermore, “there is some interest in using it to fight cancer because it seems to act specifically on certain cells,” he says.
Sugars are also connected 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.”
Source: University of Wisconsin-Madison