Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Determining the atomic structure of natural products more rapidly and accurately

22.01.2020

Many drugs are derived from natural products. But before natural products can be exploited, chemists must first determine their structure and stereochemistry. This can be a major challenge, particularly when the molecules cannot be crystallized and contain only few hydrogen atoms.

A new NMR-based method, developed at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), now simplifies the analysis and produces more accurate results. The work has been published in the Journal of the American Chemical Society.


Measuring the residual chemical shift anisotropy in a liquid crystalline medium. The method was used to determine the stereochemistry of spiroepicoccin A, a recently discovered natural product. The novel natural product was isolated from the deep-sea fungus Epicoccum nigrum, which can be found at depths of more than 4,500 meters.

Credit: Songhwan Hwang, FMP

Natural products are present in antibiotics, painkillers and cancer drugs, playing a key role in around 60 percent of all FDA approved drugs. Plants, fungi and sessile marine organisms are particularly promising sources, because many of them possess chemical defenses to deter predators. However, identification of potential drug candidates is a challenge.

First, researchers must accurately determine the structure and stereochemistry (the spatial arrangement of atoms) of the molecules. Without this information, chemists will be unable to synthesize the molecules and develop them into drugs. Moreover, the structure is needed to establish whether the molecule has previously been discovered.

Besides the X-ray diffraction method, which can only be applied to the crystallizable molecules, chemists usually use nuclear magnetic resonance (NMR) spectroscopy for structure determination. Most recently, the NMR-based parameter "residual chemical shift anisotropy" has taken on particular importance in this context.

Studies from the past two to three years have shown that this parameter facilitates the very accurate determination of the structure and stereochemistry of organic molecules. However, this requires the use of special instruments that are not available in all laboratories. And then there is the matter of the time-consuming methods of analysis involved in data analysis.

Simplified method produces more accurate results

Researchers from the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) have now developed a method that enables the residual chemical shift anisotropy to be measured much more easily and effectively.

Partners from China (Institute of Oceanology, Chinese Academy of Sciences and South Central University for Nationalities) and Brazil (Universidade Federal de Pernambuco) were also involved in the work, which has now been published in the Journal of the American Chemical Society.

"The NMR-based method we have developed enables chemists to determine the stereochemistry of novel natural products with greater accuracy and efficiency," explained Dr. Han Sun from FMP, who led the study. " Furthermore, the method is very easy to use, making it accessible to all chemists."

The experiment involves bringing together natural products with a commercially available peptide with a sequence of AAKLVFF. Dissolved in methanol, the peptides are transformed into liquid crystals, giving the natural products a weak orientation in the magnetic field.

"This particular orientation enables us to measure the residual chemical shift anisotropy of the molecules as a parameter, which in turn provides accurate information about their structure and stereochemistry," stated the chemist Sun, describing the new method.

The example of thalidomide shows how important it is to determine the stereochemistry of compounds correctly. Besides having a sedative effect (hypnotic), the compound thalidomide also has an adverse developmental effect, which is attributable to its two mirror-image forms (R)-thalidomide and (S)-thalidomide.

Analysis of exotic natural products from the ocean

For their current study, the researchers used a previously unexplored natural product: spiroepicoccin A was isolated from marine microorganisms by the Chinese partners. The substance, obtained from a depth of more than 4,500 meters, only has a few hydrogen atoms attached to its stereocenters, posing a challenge to established NMR methods. Thanks to the new measurement method, however, the structure and stereochemistry of the natural product were unambiguously elucidated.

"Even though our method enables us to measure only the relative and not the absolute stereochemistry as yet, our work makes an important contribution to simplifying the determination of challenging natural products," remarked Sun. It appears that pharmaceutical companies have already expressed an interest "because the method accelerates the development of new drugs, which is also our aim."

Media Contact

Han Sun
hsun@fmp-berlin.de
49-309-406-2902

http://www.fv-berlin.de 

Han Sun | EurekAlert!
Further information:
https://www.leibniz-fmp.de/press-media/press-releases/press-releases-single-view1/article/determining-the-atomic-structure-of-natural-products-more-rapidly-and-accurately.html
http://dx.doi.org/10.1021/jacs.9b10961

More articles from Life Sciences:

nachricht When predictions of theoretical chemists become reality
22.05.2020 | Technische Universität Dresden

nachricht From artificial meat to fine-tuning photosynthesis: Food System Innovation – and how to get there
20.05.2020 | Potsdam-Institut für Klimafolgenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: When predictions of theoretical chemists become reality

Thomas Heine, Professor of Theoretical Chemistry at TU Dresden, together with his team, first predicted a topological 2D polymer in 2019. Only one year later, an international team led by Italian researchers was able to synthesize these materials and experimentally prove their topological properties. For the renowned journal Nature Materials, this was the occasion to invite Thomas Heine to a News and Views article, which was published this week. Under the title "Making 2D Topological Polymers a reality" Prof. Heine describes how his theory became a reality.

Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other...

Im Focus: Rolling into the deep

Scientists took a leukocyte as the blueprint and developed a microrobot that has the size, shape and moving capabilities of a white blood cell. Simulating a blood vessel in a laboratory setting, they succeeded in magnetically navigating the ball-shaped microroller through this dynamic and dense environment. The drug-delivery vehicle withstood the simulated blood flow, pushing the developments in targeted drug delivery a step further: inside the body, there is no better access route to all tissues and organs than the circulatory system. A robot that could actually travel through this finely woven web would revolutionize the minimally-invasive treatment of illnesses.

A team of scientists from the Max Planck Institute for Intelligent Systems (MPI-IS) in Stuttgart invented a tiny microrobot that resembles a white blood cell...

Im Focus: NASA's Curiosity rover finds clues to chilly ancient Mars buried in rocks

By studying the chemical elements on Mars today -- including carbon and oxygen -- scientists can work backwards to piece together the history of a planet that once had the conditions necessary to support life.

Weaving this story, element by element, from roughly 140 million miles (225 million kilometers) away is a painstaking process. But scientists aren't the type...

Im Focus: Making quantum 'waves' in ultrathin materials

Study co-led by Berkeley Lab reveals how wavelike plasmons could power up a new class of sensing and photochemical technologies at the nanoscale

Wavelike, collective oscillations of electrons known as "plasmons" are very important for determining the optical and electronic properties of metals.

Im Focus: When proteins work together, but travel alone

Proteins, the microscopic “workhorses” that perform all the functions essential to life, are team players: in order to do their job, they often need to assemble into precise structures called protein complexes. These complexes, however, can be dynamic and short-lived, with proteins coming together but disbanding soon after.

In a new paper published in PNAS, researchers from the Max Planck Institute for Dynamics and Self-Organization, the University of Oxford, and Sorbonne...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

International Coral Reef Symposium in Bremen Postponed by a Year

06.04.2020 | Event News

 
Latest News

New gravitational-wave model can bring neutron stars into even sharper focus

22.05.2020 | Physics and Astronomy

A replaceable, more efficient filter for N95 masks

22.05.2020 | Materials Sciences

Capturing the coordinated dance between electrons and nuclei in a light-excited molecule

22.05.2020 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>