Reports in the May issues of Nature Structural & Molecular Biology and the Journal of Medicinal Chemistry propose answers to why it is relatively difficult for the AIDS virus to develop resistance to the drug, tenofovir, or the DAPY (diarylpyrimidine) family of compounds, and offers explanations of the mechanisms involved.
Tenofovir and the DAPY compounds are different types of reverse transcriptase (RT) inhibitors. RT is the enzyme or molecular machine the AIDS virus uses to replicate its genetic material. The two life-saving drugs approach the problem of drug resistance in different ways.
Arnold and his colleagues work on drugs that target HIV RT. "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. The research institute is jointly administered by the University of Medicine and Dentistry of New Jersey and Rutgers, The State University of New Jersey.
Since 1987, Arnold has collaborated with Stephen Hughes of the National Cancer Institute's Cancer Research and Development Center at Frederick, Md., constituting what Arnold calls "an inseparable team." Hughes is providing the biochemical analysis of the problem in conjunction with Arnold's X-ray crystallography a method by which X-ray diffraction patterns obtained from crystals are used to map the three-dimensional atomic structure of large molecules.