Featured Research

from universities, journals, and other organizations

Newly Discovered Small Molecules 'Superactivate' Botox

Date:
March 14, 2006
Source:
Scripps Research Institute
Summary:
Scientists at The Scripps Research Institute have discovered several small molecules that can "superactivate" the botulinum neurotoxin (BoNT), the commonly used cosmetic treatment for wrinkles known as Botox that has a number of therapeutic uses.

Scientists at The Scripps Research Institute have discovered several small molecules that can "superactivate" the botulinum neurotoxin (BoNT), the commonly used cosmetic treatment for wrinkles known as Botox that has a number of therapeutic uses.

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).

The study, which can be accessed online at online at http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/asap/abs/ja057699z.html, was supported by the National Institutes of Health and The Skaggs Institute for Chemical Biology.


Story Source:

The above story is based on materials provided by Scripps Research Institute. Note: Materials may be edited for content and length.


Cite This Page:

Scripps Research Institute. "Newly Discovered Small Molecules 'Superactivate' Botox." ScienceDaily. ScienceDaily, 14 March 2006. <www.sciencedaily.com/releases/2006/03/060314230145.htm>.
Scripps Research Institute. (2006, March 14). Newly Discovered Small Molecules 'Superactivate' Botox. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2006/03/060314230145.htm
Scripps Research Institute. "Newly Discovered Small Molecules 'Superactivate' Botox." ScienceDaily. www.sciencedaily.com/releases/2006/03/060314230145.htm (accessed August 1, 2014).

Share This




More Health & Medicine News

Friday, August 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Vaccine Might Be Coming, But Where's It Been?

Ebola Vaccine Might Be Coming, But Where's It Been?

Newsy (Aug. 1, 2014) Health officials are working to fast-track a vaccine — the West-African Ebola outbreak has killed more than 700. But why didn't we already have one? Video provided by Newsy
Powered by NewsLook.com
Study Links Certain Birth Control Pills To Breast Cancer

Study Links Certain Birth Control Pills To Breast Cancer

Newsy (Aug. 1, 2014) Previous studies have made the link between birth control and breast cancer, but the latest makes the link to high-estrogen oral contraceptives. Video provided by Newsy
Powered by NewsLook.com
House Republicans Vote to Sue Obama Over Healthcare Law

House Republicans Vote to Sue Obama Over Healthcare Law

Reuters - US Online Video (July 31, 2014) The Republican-led House of Representatives votes to sue President Obama, accusing him of overstepping his executive authority in making changes to the Affordable Care Act. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Uganda on Alert for Ebola but No Confirmed Cases

Uganda on Alert for Ebola but No Confirmed Cases

AFP (July 31, 2014) Uganda's health minister said on Thursday that there are no confirmed cases of Ebola in the country, but that it remained on alert for cases of the deadly virus. Uganda has suffered Ebola outbreaks in the past, most recently in 2012. Duration: 00:59 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins