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 Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>