Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Tarantula Venom Peptide Shows Promise as a Drug

15.07.2004


A tarantula venom peptide, GsMTx4, known to affect many organs, can be manipulated to withstand destruction in the stomach, making it a promising candidate for drugs that could treat cardiac arrhythmias, muscular dystrophy and many other conditions, University at Buffalo biophysicists have shown.



Moreover, the peptide, which is amphiphilic -- meaning fat-soluble on one side and water-soluble on the other, much like a detergent -- affects mechanically sensitive ion channels in membranes in a manner totally different than the standard "lock-and-key" binding mechanism.

Results of the research appear in the July 8 issue of the journal Nature.


The peptide is the only agent known to specifically block stretch-sensitive channels. Unlike other membrane channels that are sensitive to electrical potential or the binding of hormones and neurotransmitters, stretch-sensitive channels are activated by changes in membrane tension.

"Stretch-sensitive channels can play a key role in many normal tissue functions," said Tom Suchyna, Ph.D., research associate in the UB Center for Single Molecule Studies and first author on the paper. "These channels are involved in hollow-organ filling such as the bladder, in heart and circulatory-system responses to changes in blood pressure, proprioception -- knowing where your limbs and head are in space and time -- and fluid balance.

"They also are involved in abnormal tissue functions such as cardiac arrhythmias, congestive heart failure, elevated calcium levels in muscular dystrophy, and angiogenesis-supported tumor growth."

Earlier research by the UB group had shown that the novel peptide inhibits stretch-sensitive channels, but the researchers didn’t know how. To gain more information on the peptide’s possible receptor, Phillip Gottlieb, Ph.D., a co-investigator from the UB Department of Physiology and Biophysics and the Hughes Center for Single Molecule Studies, created a mirror image of the molecule, referred to as "right-handed," to observe the peptide-membrane interaction.

Since almost all proteins in nature on "left-handed," right-handed proteins won’t fit into a left-handed receptor, even if they have the same amino acid sequence. "It’s like putting your right foot into your left shoe," said Suchyna.

In this case, however, they found that both proteins inhibited stretch-sensitive channels. "If the right handed GsMTx4 works as well as the left-handed, it must be interacting with the stretch-activated channel by changing the tension that the channel senses in the membrane, rather than locking onto the channel," he said. "This leads us to believe that there is something unique about the membrane that surrounds stretch-sensitive channels, and that this special membrane environment attracts GsMTx4. That would explain why this peptide blocks only this type of channel."

In addition to providing valuable information on how the peptide works, the finding that both versions blocked the channels makes the peptide an attractive drug candidate. "This was an awesome tool to find," said Fred Sachs, Ph.D., UB professor of biophysics in the Hughes Center for Single Molecule Studies and senior author on the study.

"Peptides usually don’t make good drug candidates. They can’t be given by mouth because the stomach enzymes digest them, and they can cause an immune response. But because this peptide works in its right-handed form, and the normal left-handed digestive enzymes and left-handed antibodies don’t recognize it, oral administration is a definite possibility. It may be more than a lead compound for drug development. It may work just as it is.

"If this prognosis proves correct," said Sachs, "the peptide could be an effective treatment for atrial fibrillation, incontinence, muscular dystrophy, high blood pressure and other conditions governed by stress-sensitive channels."

Suchyna said the next steps will be to investigate the environment surrounding the channels, to study the role of stretch-activated channels in cardiac arrhythmias and to mutate the peptide to make it specific for different tissues.

Studies of these peptides on a model ion channel called gramicidin, reconstituted in artificial lipid membranes, were carried out by Sonya E. Tape, a graduate student, and Olaf S. Anderson, M.D., both from the Weill Medical College of Cornell University, and Roger E. Koeppe II, Ph.D., from the University of Arkansas.

The research was supported by grants from the National Institutes of Health.

The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York. UB’s more than 27,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs.

| newswise
Further information:
http://www.buffalo.edu

More articles from Life Sciences:

nachricht Microscope measures muscle weakness
16.11.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

nachricht Good preparation is half the digestion
16.11.2018 | Max-Planck-Institut für Stoffwechselforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Purdue cancer identity technology makes it easier to find a tumor's 'address'

16.11.2018 | Health and Medicine

Good preparation is half the digestion

16.11.2018 | Life Sciences

Microscope measures muscle weakness

16.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>