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 NTU scientists build new ultrasound device using 3-D printing technology
07.12.2016 | Nanyang Technological University

nachricht How to turn white fat brown
07.12.2016 | University of Pennsylvania School of Medicine

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: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

NTU scientists build new ultrasound device using 3-D printing technology

07.12.2016 | Health and Medicine

The balancing act: An enzyme that links endocytosis to membrane recycling

07.12.2016 | Life Sciences

How to turn white fat brown

07.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>