Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scripps Research scientists break barrier to creating potential therapeutic molecules

25.05.2010
New technique could help accelerate study and identification of new drugs

Scientists from The Scripps Research Institute have created a novel technique that for the first time will allow the efficient production of a molecular structure that is common to a vast array of natural molecules. This advance provides a means to explore the potential of this molecular substructure in the search for new therapies.

The study was published on May 23, 2010 in an advance online edition of the journal Nature Chemistry.

The structures in question, called "skipped polyenes," are shared by a large class of molecules that play a critical role in human health, including polyunsaturated fatty acids, which are vital to blood pressure regulation, inflammation, and immune response. The structures are also shared by a number of potent antibiotic, antifungal, and cytotoxic (toxic to living cells) compounds.

Simple and efficient methods for the preparation of skipped polyenes have generally been lacking, creating a significant barrier to exploring their potential as drugs. Currently, the production of molecules that contain simple variants of this substructure is quite labor intensive.

"Our study identifies a novel chemical reaction that will enable the accelerated production of this type of structural motif," said Associate Professor Glenn Micalizio, who authored the new study with a member of his Scripps Florida lab, Research Associate Todd K. Macklin. "This new reaction provides a means to explore the medicinal potential of molecules bearing complex skipped polyenes – something that we simply haven't been able to do until now."

Chemical Short Cuts

In essence, the new chemical method provides a means to replace long, step-by-step sequences of reactions that would have otherwise been required to prepare skipped polyenes. The new chemical process defines a fundamentally novel pathway (a new carbon-carbon bond forming process) to these complex structures that proceeds in just a fraction of the number of chemical steps previously required.

As such, the new method not only saves time, but greatly increases efficiency for the production of molecules that house the skipped polyene core. In chemistry, each of the steps (or reactions) used to prepare a complex structure typically proceeds with less than 100 percent efficiency, notes Micalizio—maybe 80 to 90 percent of the initial material can successfully be advanced to the next chemical step. As a result, the requirement of long sequences of reactions, where yields per step are compounded mathematically through the sequence, typically result in poor overall efficiency.

"If one can invent reactions that decrease the length of sequences required to prepare complex structures, great enhancements of efficiency can result," said Micalizio. "A central focus of our laboratory is designing new chemical reactions that do just that. Since 2005, we have been advancing a large class of chemical transformations that can be seen as 'chemical short cuts' – so that ultimately scientists can better explore the therapeutic potential of molecules inspired by the vast and diverse structures that we see in nature."

The new technique described in the Nature Chemistry paper proceeds by bond formation between two specific classes of molecules, vinylcyclopropanes and alkynes (or vinylsilanes), using a metal-promoted cross-coupling reaction to assemble the key structural motif.

"That initial metal-promoted coupling leads to a very unstable intermediate molecule," Micalizio said. "Actually, the chemical intermediate spontaneously rearranges to stabilize the structure, through a process that establishes all of the complex architecture of the skipped polyene product."

The research for the paper, "Convergent and Stereospecific Synthesis of Complex Skipped Polyenes and Polyunsaturated Fatty Acids," was supported by the American Cancer Society, the Arnold and Mabel Beckman Foundation, Boehringer Ingelheim, Eli Lilly & Co., and the National Institutes of Health.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in 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 Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Scripps Florida is located in Jupiter, Florida.

For information:
Keith McKeown
858-784-8134
kmckeown@scripps.edu

Keith McKeown | EurekAlert!
Further information:
http://www.scripps.edu

Further reports about: CHEMISTRY Nature Immunology Scripps chemical reaction fatty acid living cell

More articles from Life Sciences:

nachricht A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Switched-on DNA

20.02.2017 | Materials Sciences

Second cause of hidden hearing loss identified

20.02.2017 | Health and Medicine

Prospect for more effective treatment of nerve pain

20.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>