Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UCI scientists successfully target key HIV protein; breakthrough may lead to new drug therapies

27.09.2004


In what may be a first step toward expanding the arsenal against HIV, UC Irvine researchers have successfully targeted an HIV protein that has eluded existing therapies.



Researchers targeted Nef, a protein responsible for accelerating the development of acquired immunodeficiency syndrome, or AIDS. Nef was targeted with small molecules synthesized by the researchers – molecules that disrupted Nef’s interaction with other proteins. The technique used for identifying the synthetic molecules also may lead to new drug therapies with improved treatment options.

The researchers used a scientific technique called “phage display,” which is used to identify small molecule inhibitors that can disrupt interactions between proteins. According to Gregory Weiss, lead researcher and assistant professor in the Department of Chemistry, his research team attached the Nef protein to the surface of a harmless virus, then created synthetic molecules that could target and dislodge the protein. This is the first time phage display has been used to identify molecules that disrupt protein-protein interactions. (For more detail, see “About the Research.”)


While the method was successful, Weiss said the molecules identified proved toxic to cells. He is now seeking to develop less toxic compounds that will have high potencies against Nef without causing collateral damage. A key benefit of this achievement, he added, would be the development of therapies using smaller molecules, which can often be used in oral medications. Therapies that rely on larger molecules are used in medications injected by needle. “By proving small molecules can be effective for targeting Nef, we’ve shown how researchers can expand the fight against AIDS,” said Weiss.

The researchers reported their findings last week in the online edition of the Proceedings of the National Academy of Science. The print version of the research paper will appear in the Sept. 28 issue of the journal.

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.)

Next, the researchers looked for a mechanism that would disrupt binding by Nef. They found that their synthesized molecules and Nef both competed to bind with the cellular proteins. Each time the molecules succeeded, Nef was dislodged from binding to the three cellular proteins and thus inhibited.

Iqbal Pittalwala | EurekAlert!
Further information:
http://www.uci.edu

More articles from Life Sciences:

nachricht Polymers Based on Boron?
18.01.2018 | Julius-Maximilians-Universität Würzburg

nachricht Bioengineered soft microfibers improve T-cell production
18.01.2018 | Columbia University School of Engineering and Applied Science

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Polymers Based on Boron?

18.01.2018 | Life Sciences

Bioengineered soft microfibers improve T-cell production

18.01.2018 | Life Sciences

World’s oldest known oxygen oasis discovered

18.01.2018 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>