Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Making better medicines with a handful of chemical building blocks

20.05.2014

Soon, making and improving medical drugs could be as easy for chemists as stacking blocks is for a child.

University of Illinois chemist Martin Burke, a pioneer of a technique that constructs complex molecules from simple chemical “building blocks,” led a group that found that thousands of compounds in a class of molecules called polyenes – many of which have great potential as drugs – can be built simply and economically from a scant one dozen different building blocks.


Photo by L. Brian Stauffer

University of Illinois chemistry professor Martin Burke led a team that discovered a simple system to synthesize a large class of medically important molecules using only 12 different chemical “building blocks.”

The researchers published their findings in the journal Nature Chemistry.

“We want to understand how these molecules work, and synthesis is a very powerful engine to drive experiments that enable understanding,” said Burke, a chemistry professor at the U. of I. and the Howard Hughes Medical Institute. “We think this is a really powerful road map for getting there.

Once you have the pieces in a bottle, you can make naturally occurring molecules, or you can change the pieces slightly to make them better. Usually, that’s such a herculean task that it slows down research. But if that part becomes on-demand, you can make anything you want, and it can powerfully accelerate the drug discovery process.”

In the same way that plastic building blocks of different sizes and shapes can snap together because they share a simple connector, the chemical building blocks are linked together with one simple reaction. This gives scientists freedom to build molecules that may be difficult or expensive to extract from their natural source or to make in a lab.

One advantage of the building-block approach is that it allows the researchers to mix and match parts to build many different molecules, and to omit or substitute parts to make a potentially therapeutic substance better for human health. For example, Burke’s group recently synthesized a derivative of the anti-fungal medication amphotericin (pronounced AM-foe-TAIR-uh-sin), which led to a big breakthrough in understanding how this clinically vital but highly toxic medicine works and the discovery of another derivative that is nontoxic to human cells while still effective at killing fungus.

After their success in synthesizing derivatives of amphotericin, which fall into the polyene category, the researchers wondered, how many different building blocks would it take to make all the polyenes? (Polyene is pronounced polly-een.)

Looking at the structures of all the known naturally occurring polyenes – thousands in all – Burke and graduate students Eric Woerly and Jahnabi Roy focused on the smaller pieces that made up the molecules and found that many elements were common across numerous compounds.

After careful analysis, they calculated that more than three-quarters of all natural polyene frameworks could be made with only 12 different blocks.

“That is the key most surprising result,” Burke said. “We’ve had this gut instinct that there will be a set number of building blocks from which most natural products can be made. We’re convinced, based on this result, that we can put together a platform that would enable on-demand assembly of complex small molecules. Then researchers can focus on exploring the function of these molecules, rather than spending all their time and energy trying to make them.”

Watch a video of Burke explaining the building block approach.

To demonstrate this surprising finding, the researchers synthesized several compounds representing a wide variety of polyene molecules using only the dozen designated building blocks. Many of these building blocks are available commercially thanks to a partnership between Burke’s group and Sigma-Aldrich, a chemical company.

Burke hopes that identifying the required building blocks and making them widely available will speed understanding of polyene natural products and their potential as pharmaceuticals, particularly compounds that until now have been left unexplored because they were too costly or time-consuming to make.

Burke’s group hopes eventually to identify and manufacture a set of building blocks from which any researcher – trained chemist or not – can build any small molecule.

“Now that we have this quantifiable result, that with only 12 building blocks we can make more than 75 percent of polyenes, we are committed to figuring out a global collection of building blocks – how to make them, how to put them together – to create a generalized approach for small-molecule synthesis.”

The National Institutes of Health supported the work.

Editor's note: To contact Martin Burke, call 217-244-8726; email mdburke@illinois.edu.

The paper, “Synthesis of most polyene natural product motifs using just 12 building blocks and one coupling reaction,” is available online.

Liz Ahlberg | University of Illinois
Further information:
http://www.illinois.edu

Further reports about: compounds drugs energy function medicines plastic structures synthesis

More articles from Life Sciences:

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers shoot for success with simulations of laser pulse-material interactions

29.03.2017 | Materials Sciences

Igniting a solar flare in the corona with lower-atmosphere kindling

29.03.2017 | Physics and Astronomy

As sea level rises, much of Honolulu and Waikiki vulnerable to groundwater inundation

29.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>