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.
Liz Ahlberg | University of Illinois
What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society
Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
23.08.2017 | Life Sciences
23.08.2017 | Life Sciences
23.08.2017 | Physics and Astronomy