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

ponents."

That change in physical properties effectively cloaks the arginine-Taxol complex, allowing it to slip past the sentries and into the cell. As it passes into the cell, the weak bonds it formed with the membrane components break and the transporter, with its therapeutic load, is free to roam inside the cell.

But after getting into the cell, the arginine-Taxol complex still has to break apart for the Taxol to do its job against the cancer cell. Wender's group achieved this by taking advantage of the presence of a molecule called glutathione, which is generally abundant inside cells and which in cancer cells tends to be present in higher levels than usual.

Glutathione is predisposed to attacking sulphur-sulphur bonds, so that is the bond the researchers used to hold the arginine and Taxol together. Once the arginine-Taxol complex is inside the cell, the glutathione can get to work hacking away at the sulphur bonds, and in the process, unwittingly release the compound that will spell its doom.

Because glutathione is relatively scarce outside of cells, the arginine transporter is effectively inert in that environment, so there are no side effects from having the arginine-Taxol complex moving through the patient's body. This is in stark contrast to the present situation, as many patients are extremely sensitive to the molecular vehicle that is currently used to administer ferried Taxol to the cancer cells.

The researchers achieved another breakthrough by tinkering with the form of the arginine used in their transporter. By altering certain aspects of the arginine, the researchers were able to control the rate at which glutathione slices and dices the arginine-Taxol complex.

This gives them an unprecedented ability to regulate the amount of medication that is active inside the patient at any point in time. To date, doctors have had to be content with injecting as high a dose of medication as patients can tole
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Contact: Louis Bergeron
louisb3@stanford.edu
650-725-1944
Stanford University
Source:Eurekalert

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