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 Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Self-illuminating pixels for a new display generation

22.05.2018 | Trade Fair News

Embryonic development: How do limbs develop from cells?

22.05.2018 | Life Sciences

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>