Human immunodeficiency virus, commonly known as HIV, is known to cause AIDS. The virus attacks the body's immune system, making the body vulnerable to infections and certain cancers. Symptoms of acute HIV infection may include fever, headache, fatigue and enlarged lymph nodes. The virus is spread most commonly by having unprotected sex with an infected person.
Funded by the Arnold and Mabel Beckman Foundation, the Burroughs Wellcome Fund and the National Institutes of Health, the three-year research effort involved innovation in small molecule discovery. Conducted entirely at UCI, the multidisciplinary research involved a partnership among three laboratories and a collaboration of scientists in chemistry, molecular biology, biochemistry and pathology.
Besides Weiss, co-authors of the study are Allison Olszewski, Ken Sato, Zachary D. Aron, Frederick Cohen, Aleishia Harris, Brenda R. McDougall, W. Edward Robinson Jr., and Larry Overman. Olszewski, a doctoral candidate in chemistry, is the lead author of the paper. Overman's laboratory synthesized the small molecules; Robinson's laboratory tested them for cellular toxicity and anti-HIV activity; and Weiss' laboratory performed measurements to identify which molecules were inhibitory to Nef.
ABOUT THE RESEARCH:
Led by chemist Gregory Weiss, the researchers invented a system for identifying guanidine alkaloids small molecule inhibitors of protein-protein interactions. They attached the Nef protein to the surface of a bacteriophage (a virus whose host is a bacterium), which provided a 'handle' that could be tracked by the researchers to determine whether Nef was binding to three cellular proteins, as is Nef's function. (Although Nef is able to bind well to the three proteins in the absence of the bacteriophage, the researchers used the bacteriophage simply as a handle to watch the binding.)
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Contact: Iqbal Pittalwala
iqbal@uci.edu
949-824-3969
University of California - Irvine
24-Sep-2004