Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Turning green gunk to gold, anti-cancer gold

11.01.2007
Combining synthetic chemistry techniques with a knowledge of the properties and actions of enzymes, scientists have been able to produce an exciting class of anti-cancer drugs originally isolated from blue-green algae.

This accomplishment is expected to make it possible to produce enough of the promising drugs for use in clinical trials.

In a study featured on the cover of the January issue of the journal ACS Chemical Biology, a scientific team lead by University of Michigan Life Sciences Institute Research Professor David H. Sherman and researcher Zachary Q. Beck found the trick to turning the green gunk into gold—cancer fighting gold.

"It was simply too difficult to use the native blue-green algae for high-level production using traditional fermentation approaches," said Sherman. But the compound, called cryptophycin 1, held so much promise as an anti-cancer drug that organic chemists got busy trying to find ways to make a synthetic form of the compound in large enough quantities for clinical trials.

Developing an efficient synthetic route to natural product compounds and their analogs is often an essential step in drug development. With drugs such as penicillin and tetracycline, it can easily be done, but cryptophycins present more of a challenge. Sherman's team realized that with all cryptophycins, the most difficult step came very late in the synthesis, at the point at which a key part called an epoxide—a highly strained, three-membered ring oxygen-containing group, crucial for the drug's anti-cancer activity—becomes attached to the molecule.

The epoxide group can be attached in two configurations, designated as alpha and beta. Scientists have known for several years that the beta configuration was absolutely required for the anti-cancer properties of the drug, but were unable to devise efficient synthetic strategies that favored that configuration.

Sherman's team accomplished this by isolating the entire set of biosynthetic genes and key enzymes and developing a new, efficient method to manufacture the broad class of cryptophycin natural products, including important analogs with clinical potential. This included characterization of an enzyme, cytochrome P450, that always introduces the epoxide in the desired beta configuration.

Sherman, who is also the John G. Searle Professor of Medicinal Chemistry in the College of Pharmacy, believes that this approach will allow effective new cryptophycin analogs with low levels of side effects to be created for clinical trials.

"This issue represented an exciting target that offered not only an interesting scientific problem, but the potential to do something of practical importance in creating a promising anti-cancer drug," he said.

"Biosynthetic Characterization and Chemoenzymatic Assembly of the Cryptophycins. Potent Anticancer Agents from Nostoc Cyanobionts" by Magarvey N. A.; Beck Z. Q.; Golakoti T. ; Ding Y. ; Huber U. ; Hemscheidt T. K.; Abelson D. ; Moore R. E.; Sherman D. H. appeared online Dec.15 and is the cover story in the print version of ACS Chemical Biology January, 2007.

Robin Stephenson | EurekAlert!
Further information:
http://www.umich.edu

Further reports about: Configuration anti-cancer cryptophycin synthetic

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 >>>