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New method to overcome multiple drug resistant diseases developed by Stanford researchers
Date:8/18/2008

e pumps are occupied with the decoy molecule. But if any of the molecules make their way into healthy cells, they can gum up the proper functioning of the pumps in those cells, too, adding to the litany of undesirable side effects that generally accompany chemotherapy.

Wender's group decided to see if they could take drugs to which diseases had become resistant and, by combining them with what they call "molecular transporters," get them in around the pump.

"If we think of the pump as being a bouncer for the cellular club, then effectively what we're doing is disguising one of these therapeutic agents to get it in through the back door or the side door," Wender said. "We're not even going to deal with the bouncer."

Therein lies what may be the greatest value of the work. The basic approach of bonding a medication to an arginine-rich transporter to slip it past the cellular sentries could, in theory, be used to get any of a host of medications into any cell that has developed the type of resistance involving increased numbers of export pumps.

"This could potentially be used with any drug which is effective but has a delivery problem," Teng said. "Not just Taxol."

That could include medications for diseases caused by antibiotic resistant bacteria, such as multi-drug resistant tuberculosis, or by drug resistant parasites such as malaria, as well as other types of cancer.

The arginine transporter manages to avoid ejection by slipping through the membrane of the cell in between the pumps. The key is the ability of arginine to form weak, temporary bonds with some of the molecules that reside in the membrane.

"As the transporter, with all these arginine guanidinium groups, approaches the cell, it basically does a handshake using hydrogen bonds with cell surface constituents that are in the membrane," Wender said. "In essence, it changes its physical properties by shaking hands with all these cell membrane com
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Contact: Louis Bergeron
louisb3@stanford.edu
650-725-1944
Stanford University
Source:Eurekalert

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