Monday, 11 September 2017

APPLICATION OF DNA SEQUENCING IN ORGANIC SYNTHESIS

Mateja Klika Škopić et al, Chem. Sci, 2017, DOI: 10.1039/C7SC00455A

It was found that 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 the publication, the researchers have identified a particular section of DNA – a nucleoside called thymidine – which is astonishingly stable to harsh reaction conditions.
They 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, they broaden the scope of drug-like structures that can be accessed using this method.
They reported that, 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 the 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.

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