New Research
Fighting HIV drug resistance with new compounds
Archived article from Sep 20, 2004
HIV is a moving target, unpredictably changing direction to elude anti-AIDS drugs, but researchers are clearly on the track of solutions to combat HIV drug resistance.
Leading a multidisciplinary ensemble of colleagues, Edward Arnold, professor of chemistry in New Brunswick, works on drugs that target HIV reverse transcriptase (RT) –the enzyme or molecular machine the AIDS virus uses to replicate its genetic material.
“We try to understand how these drugs work, and how they may be able to evade resistance mechanisms, so that we can apply the information to the design of better drugs,” said Arnold, a resident faculty member of the Center for Advanced Biotechnology and Medicine.
Tenofovir and the DAPY (diarylpyrimidine) family of compounds are different types of RT inhibitors that approach the problem of drug resistance in different ways.
HIV-RT uses ingredients available within the cell as building blocks to make the genetic copies allowing the virus to proliferate. The tenofovir molecule is slightly smaller than normal building blocks, which enables it to substitute for those the RT is trying to use.
Because tenofovir is smaller, it is difficult for RT to learn to distinguish it from the normal building blocks and develop resistance to the drug. The DAPY family of compounds works differently, attaching to a site near the heart of the RT molecular machine, blocking its activity.
“It’s like throwing a molecular monkey wrench into the virus’s essential machinery,” Arnold said. “The conclusions we have drawn do not represent an endpoint, but rather punctuation marks – places where we have achieved some significant milestones that will help guide us in the design of new and more effective anti-AIDS drugs.”
– Joseph Blumberg
Return to the Sep 20, 2004 issue
|
