Featured Research

from universities, journals, and other organizations

A 'Periodic Table' Of Natural Products

Date:
November 29, 2005
Source:
Max Planck Society
Summary:
Natural products have always been an important source for the development of chemical tool compounds or drugs respectively in chemical biology and pharmaceutical research. Scientists from the Max Planck Institute of Molecular Physiology in Dortmund, Germany have now described the structural interrelationships between natural products by analyzing some 200,000 of them in co-operation with scientists from the pharmaceutical company Novartis in Basel, Switzerland.

The new structural classification of natural products, SCONP (Structural Classification Of Natural Products).
Credit: Image : Max Planck Institute of Molecular Physiology

Natural products have always been an important source for the development of chemical tool compounds or drugs respectively in chemical biology and pharmaceutical research. Researchers frequently build up what are known as "combinatorial libraries" based on the structural characteristics of natural products. Scientists from the Max Planck Institute of Molecular Physiology in Dortmund, Germany have now described the structural interrelationships between natural products by analyzing some 200,000 of them in co-operation with scientists from the pharmaceutical company Novartis in Basel, Switzerland. This analysis led to a new classification of natural products based on their structure, called SCONP (Structural Classification Of Natural Products). Guided by SCONP, the researchers developed a new structural class of inhibitors of 11b-hydroxysteroid dehydrogenase type 1. Inhibition of this enzyme is being discussed as a promising approach for the treatment of obesity, the metabolic syndrome, diabetes type 2, and cognitive dysfunction. (PNAS, Early Edition, November 21, 2005)

Related Articles


Scientists working with Professor Herbert Waldmann have been focusing their interest on biologically relevant starting points for the targeted development of drug-like molecules capable of influencing the function of disease-related proteins. Natural products are particularly well-suited to be such starting points. They are produced for very specific biological purposes by the respective organism. Natural products play a role in chemical defence and communication.

Natural products are synthesized by specific enzymes and, over the course of evolution, have been optimized for their particular function. The chemical structures of natural products are thus "privileged" in the sense that they are part of the "chemical space", used by nature for small organic molecules. One can imagine the totality of all thinkable chemical structures as an infinite space, not unlike our universe. In this picture, single chemical molecules represent "stars" and groups of molecules "galaxies".

The researchers in Dortmund, in co-operation with Novartis, have investigated the scaffolds of natural products and then classified them hierarchically, by scaffold size and complexity, into a tree-like diagram (see image 1). The scientists generated structure-based "genealogies" of the natural product scaffolds and correlated them with each other. Each natural product scaffold was thus traced back to a one ring scaffold as a single unit.

This yielded a kind of phylogenetic tree. Its scaffolds are classified exclusively on the basis of structural similarities and the number of rings in the scaffold. Every node in the tree diagram represents a certain scaffold. From such a node several branches may lead to nodes representing more complex scaffolds. This scaffold-based structural classification of natural products was, at each node, annotated with the biological source organism, and the biological effect, as far as it was known. In this way the researchers have developed the first exclusively structure-based ordering principle for natural products ("Structural Classification Of Natural Products", or SCONP). It can help us navigate the "chemical space" of natural products.

The researchers used SCONP together with PSSC as a secondary criterion. It is a concept that groups proteins on the basis of structural similarity. This allowed the development of structurally simplified, but effective and highly selective, inhibitors of the enzyme 11bHSD. The starting point was the complex natural product and non-selective 11bHSD inhibitor, glycyrrhetinic acid (1, see image 2).

The analysis proceeded as follows. The scaffold of glycyrrhetinic acid (1) was assigned to the appropriate node in the SCONP tree. "Brachiation" within the SCONP tree toward the roots - that is, in the direction of simpler scaffolds - led to a group of two, three, and four ring scaffolds, which appear most frequently in nature. This finding is based on a statistical analysis of the frequency of occurrence of the natural product scaffolds. Out of this subset of natural product scaffolds, and using PSSC as a second, independent criterion, the researchers chose the octahydronaphthaline scaffold, which is also found in the natural product dysidiolide (2, see image 2).

Based on this analysis they built up a collection of 162 compounds with octahydronaphthaline scaffold. They further investigated whether the compounds could inhibit the enzyme 11bHSD1. In total, 30 different inhibitors could be identified in the compound library. Four of them inhibited the enzyme in the nanomolar range. Cellular activity of this new structural class of 11bHSD1 inhibitors could be shown with the most active and selective compound (3, image 2).

The researchers now plan to refine their classification concept, and they hope to give more examples of how to use this concept for the development of new chemical tool compounds and drugs.


Story Source:

The above story is based on materials provided by Max Planck Society. Note: Materials may be edited for content and length.


Cite This Page:

Max Planck Society. "A 'Periodic Table' Of Natural Products." ScienceDaily. ScienceDaily, 29 November 2005. <www.sciencedaily.com/releases/2005/11/051129190247.htm>.
Max Planck Society. (2005, November 29). A 'Periodic Table' Of Natural Products. ScienceDaily. Retrieved October 24, 2014 from www.sciencedaily.com/releases/2005/11/051129190247.htm
Max Planck Society. "A 'Periodic Table' Of Natural Products." ScienceDaily. www.sciencedaily.com/releases/2005/11/051129190247.htm (accessed October 24, 2014).

Share This



More Matter & Energy News

Friday, October 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

3D Printed Instruments Make Sweet Music in Sweden

3D Printed Instruments Make Sweet Music in Sweden

Reuters - Innovations Video Online (Oct. 23, 2014) Students from Lund University's Malmo Academy of Music are believed to be the world's first band to all use 3D printed instruments. The guitar, bass guitar, keyboard and drums were built by Olaf Diegel, professor of product development, who says 3D printing allows musicians to design an instrument to their exact specifications. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Chameleon Camouflage to Give Tanks Cloaking Capabilities

Chameleon Camouflage to Give Tanks Cloaking Capabilities

Reuters - Innovations Video Online (Oct. 22, 2014) Inspired by the way a chameleon changes its colour to disguise itself; scientists in Poland want to replace traditional camouflage paint with thousands of electrochromic plates that will continuously change colour to blend with its surroundings. The first PL-01 concept tank prototype will be tested within a few years, with scientists predicting that a similar technology could even be woven into the fabric of a soldiers' clothing making them virtually invisible to the naked eye. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Jet Sales Lift Boeing Profit 18 Pct.

Jet Sales Lift Boeing Profit 18 Pct.

Reuters - Business Video Online (Oct. 22, 2014) Strong jet demand has pushed Boeing to raise its profit forecast for the third time, but analysts were disappointed by its small cash flow. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Internet of Things Aims to Smarten Your Life

Internet of Things Aims to Smarten Your Life

AP (Oct. 22, 2014) As more and more Bluetooth-enabled devices are reaching consumers, developers are busy connecting them together as part of the Internet of Things. (Oct. 22) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Space & Time

Matter & Energy

Computers & Math

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins