Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

High resolution ’snapshots’ detail dynamics of a cocaine antibody

10.02.2006


Information may spur new therapeutic approaches to addiction and abuse



Cocaine-binding antibodies have shown some promise in their ability to neutralize cocaine toxicity, but their binding ability is severely impaired by high concentrations of the drug. A catalytic monoclonal antibody such as 7A1, on the other hand, has the ability to regenerate after each new dose of the drug, making it far more effective than others in metabolizing cocaine.

The study, which will be published in the February issue (Volume 14 Issue 2) of the journal Structure, was led by Ian A. Wilson, D.Phil., of Scripps Research Department of Molecular Biology and The Skaggs Institute for Chemical Biology, and Kim D. Janda, Ph.D., of Scripps Research Departments of Chemistry and Immunology and The Skaggs Institute for Chemical Biology.


Despite intensive research, cocaine abuse continues to be a major public health problem, so far eluding efforts at developing an effective therapeutic agent to counter the craving, addiction, and overdose of the drug. To date, no treatment has been approved by the Food and Drug Administration (FDA).

Commenting on the new findings, Xueyong Zhu, Ph.D., the primary author of the study and a staff scientist in the Wilson laboratory said, "Development of effective therapies for cocaine abuse has been a long-standing goal, and a number of medications under study do show some promise. Immunopharmacotherapy has been proposed as a way to neutralize the drug outside the central nervous system- basically soaking up the drug before it has a chance to cross the blood brain barrier-as a potentially effective new approach to treat cocaine abuse."

Using a monoclonal antibody endowed not only with high binding ability, but also with sufficient catalytic activity to metabolize cocaine, would have potentially enhanced therapeutic effects, Zhu said. This antibody could intercept cocaine in the blood stream before it reaches the central nervous system-stopping the drug cold. Because cocaine has a half life of approximately 30 minutes inside the human body, a cocaine catalytic antibody would basically have to out-run the body’s natural metabolism process to have any serious impact on the psychoactive effects of the drug.

Generated by x-ray crystallography, pictures of the conformational changes that occur during the antibody’s complete catalytic cycle show the molecular basis for catalysis and reveal possible mutations that could increase catalytic proficiency. This, Zhu pointed out, provides a foundation for the humanization and mutagenesis of the antibody to enhance its cocaine-hydrolyzing activity and make future human clinical trials feasible. "Given the fact that catalytic antibodies have been produced with the same levels of efficiency as natural enzymes, it seems well within the realm of possibility," he added.

To reach this ambitious goal, however, it may be necessary to explore new incremental approaches for optimizing the efficiency of such catalytic activity. Novel functional groups could be introduced into first generation antibody catalysts by multiple rounds of mutagenesis and selection to produce improvements. In essence, this would allow scientists to dramatically accelerate the evolutionary process, producing improvements in the immune system in weeks or months that previously took billions of years.

"The structural insights into antibody catalysis that we have shown with 7A1 Fab’ are critical for any future improvement of effective biocatalysts," Zhu said. "One of the main goals of our lab has been to focus on catalytic antibodies that will have a direct impact on public health issues. With the snapshots of the complete cycle of the cocaine antibody catalytic reaction, we have shed new light on the sequence of events in an antibody-mediated reaction and provided a rare glimpse of the structural dynamics involved. With this information, it’s possible to move onto the next step in the development of a treatment for cocaine abuse and addiction."

Keith McKeown | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Health and Medicine:

nachricht Penn study identifies new malaria parasites in wild bonobos
21.11.2017 | University of Pennsylvania School of Medicine

nachricht NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Previous evidence of water on mars now identified as grainflows

21.11.2017 | Physics and Astronomy

NASA's James Webb Space Telescope completes final cryogenic testing

21.11.2017 | Physics and Astronomy

New catalyst controls activation of a carbon-hydrogen bond

21.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>