Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Newly discovered small molecules

16.03.2006


Findings could increase popular compound’s therapeutic use and effectiveness



According to the study, these activators bind to specific sites on the neurotoxin protein, increasing protease activity and enhancing the toxin’s effect. In some cases, the study noted, the activation power of the new molecules was as much as fourteen-fold, the greatest increase in activation ever reported for a protease; before this study, a two-fold activation of a protease was referred to as a state of "superactivation." Proteases are enzymes that act as cellular catalysts, breaking up proteins into smaller elements such as amino acids and reducing the amount of energy needed for the activation.
The study was released in an advanced online version by the Journal of the American Chemical Society.

Kim Janda, currently the Ely R. Callaway Jr. professor of chemistry, director of the Worm Institute for Research and Medicine (WIRM), and head of the laboratory that conducted the study, said, "Since the botulinum neurotoxin is the most poisonous toxin known, finding a compound to activate it might seem somewhat counterproductive. But the range of clinical uses for the toxin have increased well beyond its cosmetic use--multiple sclerosis, stroke, cerebral palsy, migraine, and backache are just a few of the conditions for which BoNT has proven surprisingly effective. The discovery of small molecule activators may ultimately provide a valuable method for minimizing dosage, reducing resistance, and increasing its clinical efficacy."



Botulinum neurotoxins are the most lethal poisons known. They produce progressive paralysis by binding to nerves at the point where they connect to muscles, and blocking the release of acetylcholine, which signals the muscles to contract, including those that regulate breathing. Blocking the nerve signal results in paralysis and, unless treated quickly, death. A lethal dose is small--eight tenths of an inhaled microgram for a 175-pound person.

Because of its highly potent neurotoxic activity, Janda added, the use of BoNT is also of substantial global concern as a potential bioterrorist weapon.

One of the main drawbacks associated with BoNT as a therapeutic is that repeated use can lead to the development of a significant immune response. Tolerance to it develops most rapidly when patients receive frequent high doses of the toxin.

"We hypothesized that the use of BoNT in combination with a small molecule that could superactivate the action of the toxin would allow for lower doses," Janda said, "and reduce the patient’s immune response. As the importance of BoNT in medicine continues to expand, we need to find some way to counter these unintended immune responses. Compounds like the ones we discovered, which produced the greatest protease activation ever recorded, may point the way to a potential solution."

Other authors of the study include Laura A. McAllister, Mark S. Hixon, Jack P. Kennedy, and Tobin J. Dickerson, all of the Scripps Research Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, and Worm Institute for Research and Medicine (WIRM).

About The Scripps Research Institute

The Scripps Research Institute, headquartered in La Jolla, California, in 18 buildings on 40 acres overlooking the Pacific Ocean, is one of the world’s largest independent, non-profit biomedical research organizations. It stands at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel.

Scripps Florida, a 364,000 square-foot, state-of-the-art biomedical research facility, will be built in Palm Beach County. The facility will focus on basic biomedical science, drug discovery, and technology development. Palm Beach County and the State of Florida have provided start-up economic packages for development, building, staffing, and equipping the campus. Scripps Florida now operates with approximately 160 scientists, technicians, and administrative staff at 40,000 square-foot lab facilities on the Florida Atlantic University campus in Jupiter.

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

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>