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 Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>