DNA sequencing in organic synthesis
Under the covers
Tagging drug-like small molecules with short individual DNA 'barcode' strands makes them identifiable by DNA sequencing. Andreas Brunschweiger, of Technische Universität Dortmund, and artist Cornelia Janda explain their cover on Chemical Science.
Andreas: DNA sequencing offers fascinating new methods of carrying out drug research. It makes it possible to put a large number of organic chemical compounds in a single test-tube, tagged with different DNA sequences, and follow them throughout the reaction, ultimately identifying which of them might bind to a disease-relevant protein.
The problem is that DNA is often unstable under the reaction conditions used to make drugs. In our publication, we have identified a particular section of DNA – a nucleoside called thymidine – which is astonishingly stable to harsh reaction conditions.
We therefore use a short thymidine sequence, called hexathymidine or hexT, as a chemotolerant adapter for tagged small molecule synthesis. By appending hexT to DNA 'barcode' sequences, we broaden the scope of drug-like structures that we can access using this method.
From the art desk
Cornelia: It was challenging to capture a complex process in a single picture. At first, I experimented with a machine, but that would not have conveyed the synthesis and encoding process properly.
The leitmotif of this research area is the population of chemical space by collections of molecules so I decided to use the space motif as background. In the foreground, I placed two astronauts to illustrate that the process of synthesizing these collections really consists of two steps: One astronaut holds a tool, a catalyst, in his hand. He receives a starting material tagged with a short hexathymine DNA sequence, and uses his tool to synthesize the target molecule.
Following synthesis, he hands the molecule over to the next astronaut who glues a DNA strand consisting of a code and a hexaadenine sequence to the hexathymidine-small molecule structure with a tool called “T4”, which is an enzyme that connects DNA fragments. The products of this procedure are then populating the (chemical) space.
Finding the appropriate stock picture for this idea was a hard task. Therefore, we joined nine separate images together. I drew the transitions and retouches by hand in Photoshop. Unfortunately, I do not have my original sketches any more – but they looked like the fondly scribbled drawings of a kindergartener.
Read the article
Mateja Klika Škopić et al, Chem. Sci, 2017, DOI: 10.1039/C7SC00455A
This image appears on the front cover of Chemical Science, 2017, Issue 5.
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