Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Uncover Key Trigger for Potent Cancer-Fighting Marine Product

08.01.2008
Discovery could lead to new versions of drug being tested as a cancer treatment in humans

Scripps Institution of Oceanography/UC San Diego

An unexpected discovery in marine biomedical laboratories at Scripps Institution of Oceanography at UC San Diego has led to new, key information about the fundamental biological processes inside a marine organism that creates a natural product currently being tested to treat cancer in humans. The finding could lead to new applications of the natural product in treating human diseases.

A research team led by Bradley Moore, a professor with UCSD's Scripps Oceanography Center for Marine Biotechnology and Biomedicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, and postdoctoral researcher Alessandra Eustáquio, along with their colleagues at The Salk Institute for Biological Studies, discovered an enzyme called SalL inside Salinispora tropica, a promising marine bacterium identified in 1991 by Scripps researchers.

... more about:
»Marine »Scripps »chlorine »natural

As they describe in the most recent issue of Nature Chemical Biology, the researchers also identified a novel process-a "pathway"-for the way the marine bacterium incorporates a chlorine atom, the key ingredient for triggering its potent cancer-fighting natural product. Previously known methods for activating chlorine were processed through oxygen-based approaches. The new method, on the other hand, employs a substitution strategy that uses non-oxidized chlorine as it is found in nature, as with common table salt.

"This was a totally unexpected pathway," said Moore. "There are well over 2,000 chlorinated natural products and this is the first example in which chlorine is assimilated by this kind of pathway," said Moore.

The Salinispora derivative "salinosporamide A" is currently in phase I human clinical trials for the treatment of multiple myeloma and other cancers. A team led by Moore and Scripps' Daniel Udwary solved the genome of S. tropica in June, an achievement that helped pave the way for the new discoveries.

Moore believes the discoveries provide a new "road map" for furthering S. tropica's potential for drug development. Knowing the pathway of how the natural product is made biologically may give biotechnology and pharmaceutical scientists the ability to manipulate key molecules to engineer new versions of Salinispora-derived drugs. Genetic engineering may allow the development of second-generation compounds that can't be found in nature.

"It's possible that drug companies could manufacture this type of drug in greater quantities now that we know how nature makes it," said Moore.

At this point it is unclear how pervasively SalL and its unique biological activation pathway exist in the ocean environment. Chlorine is a major component of seawater, and, according to Moore, a fundamental component of Salinispora's disease-inhibiting abilities. Salinosporamide A, for example, is 500 times more potent than its chlorine-free analog salinosporamide B.

"The chlorine atom in salinosporamide A is key to the drug's irreversible binding to its biological target and one of the reasons the drug is so effective against cancer," said Moore.

According to Eustáquio, finding the enzyme and its new pathway also carries implications for understanding evolutionary developments, including clues for how and why related enzymes are activated in different ways.

Also joining Moore and Eustáquio in the research were coauthors Florence Pojer and Joseph Noel (of the Howard Hughes Medical Institute, Jack H. Skirball Center for Chemical Biology and Proteomics, The Salk Institute for Biological Studies), who developed high-resolution X-ray structures and other aspects of the research.

The work was supported by the National Oceanic and Atmospheric Administration, the National Institutes of Health and the National Science Foundation.

Mario Aguilera | EurekAlert!
Further information:
http://www.ucsd.edu

Further reports about: Marine Scripps chlorine natural

More articles from Life Sciences:

nachricht Researchers target protein that protects bacteria's DNA 'recipes'
21.08.2018 | University of Rochester

nachricht Protein interaction helps Yersinia cause disease
21.08.2018 | Schwedischer Forschungsrat - The Swedish Research Council

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.

The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Air pollution leads to cardiovascular diseases

21.08.2018 | Ecology, The Environment and Conservation

Researchers target protein that protects bacteria's DNA 'recipes'

21.08.2018 | Life Sciences

A paper battery powered by bacteria

21.08.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>