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Mimicking natural evolution with 'promiscuous reactions' to improve the diversity of drugs
Date:8/24/2014

er set of experiments. Only at the end, when we have something really good, do we work out exactly what we have made."

In the study, the researchers investigated the reactions of 12 types of an organic molecule called a 'diazo' compound. The researchers chose to study reactions of diazo compounds as they have many possible outcomes, depending on the specific reaction conditions (such as the temperature and concentrations used) and the choice of the reaction catalyst.

Different types and quantities of the reaction 'ingredients' were added to each of the 96 wells of an experiment tray and the products of the reaction were then tested to see if they had the required biological effect.

"The key to our method is using very promiscuous reactions which can lead to many different interesting products. Normally, these are the sort of reactions that chemists would steer well clear of, but in this case it's actually an advantage and gives us the chance of finding some diverse and active structures," said Dr Warriner.

To assess the effectiveness of the reaction products as drugs, the researchers studied how well they could activate a particular biologically relevant protein called the 'androgen receptor', which is important in the progression of certain cancers.

The results informed two further rounds of experiments on the most promising candidates, from which the researchers eventually identified three biologically active molecules.

"It's very unlikely that anyone would have ever designed these molecules or thought to use these compound classes against this target, but we have reached that result very efficiently and rapidly using our methodology," said Karageorgis.

Professor Adam Nelson from the School of Chemistry and the Astbury Centre for Structural Molecular Biology at the University of Leeds, a co-author on the paper, concludes: "The beauty of our approach is that pharmaceutical companies could start using i
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Contact: Sarah Reed
s.j.reed@leeds.ac.uk
44-011-334-34196
University of Leeds
Source:Eurekalert

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