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

A revolutionary new scientific method developed at the University of Leeds will improve the diversity of 'biologically active molecules', such as antibiotics and anti-cancer agents.

The researchers, who report their findings online today in the journal Nature Chemistry, took their inspiration from evolution in nature. The research may uncover new pharmaceutical drugs that traditional methods would never have found.

"Nature produces some amazing structures with really interesting biological activity, but the plant or animal did not design them. Instead the organisms gradually evolved both the chemical structures and the methods to produce them over millennia because they were of benefit. We wanted to capture the essence of this in our approach to discovering new drugs," said George Karageorgis, a PhD student from the School of Chemistry and the Astbury Centre for Structural Molecular Biology at the University of Leeds, and first author of the study.

The traditional method for discovering new drugs involves preparing new biologically active molecules by adjusting the chemical structure of an existing one slightly and analysing the results. This trial and error method is both time consuming and limits the variety of new types of drugs that are developed.

"There is a known problem with limited diversity in drug discovery. It's like a baker always going to the same storage cupboard and using the same ingredients, yet hoping to create something that tastes different," said Dr Stuart Warriner from the School of Chemistry and the Astbury Centre for Structural Molecular Biology at the University of Leeds, a co-author of the research paper.

"Our novel approach is like taking lots of different ingredients including things you may never think will work together and trying different combinations of these in each cup of a cupcake tray. If the result 'tastes' promising then we use this as the starting point for another 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 it tomorrow, as you don't need any specialist equipment. What we need to do now is to run further studies and add even more diversity to the potential products of our reactions to convince other scientists to adopt this new technique."


'/>"/>

Contact: Sarah Reed
s.j.reed@leeds.ac.uk
44-011-334-34196
University of Leeds
Source:Eurekalert

Related biology news :

1. Mimicking living cells: Synthesizing ribosomes
2. Combinations of estrogen-mimicking chemicals found to strongly distort hormone action
3. Penn team mimicking a natural defense against malaria to develop new treatments
4. EU FET program funds research on 3D neuronal structures mimicking human brain tissue
5. Hormone-mimicking chemicals cause inter-species mating
6. A semi-artificial leaf faster than natural photosynthesis
7. How long does it take to make a natural fracture?
8. The Rim Fire 1 year later: A natural experiment in fire ecology and management
9. Natural-terrain schoolyards reduce childrens stress, says Colorado University-Boulder study
10. A natural way to monitor, and possibly control populations of, stink bugs
11. Mouse study: Natural birth may strengthen the immune system
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/13/2017)... UBM,s Advanced Design and Manufacturing event in ... and evolving technology through its 3D Printing and Smart ... the expo portion of the event and feature a ... on trending topics within 3D printing and smart manufacturing. ... will take place June 13-15, 2017 at the Jacob K. ...
(Date:4/11/2017)... 11, 2017 No two people are ... the New York University Tandon School of Engineering ... found that partial similarities between prints are common ... mobile phones and other electronic devices can be ... vulnerability lies in the fact that fingerprint-based authentication ...
(Date:4/5/2017)... , April 5, 2017 Today HYPR ... that the server component of the HYPR platform is ... providing the end-to-end security architecture that empowers biometric authentication ... HYPR has already secured over 15 million users across ... manufacturers of connected home product suites and physical access ...
Breaking Biology News(10 mins):
(Date:9/21/2017)... ... September 21, 2017 , ... Today, ... professionals, has announced the addition of 5 new courses to its prospectus. These ... with Regulation 21 CFR Part 11 on Electronic Records and Electronic Signatures (Part ...
(Date:9/21/2017)... ... September 21, 2017 , ... Lajollacooks4u welcomed the San Diego chapter ... a worldwide society of professional women with high achievement in the fields of food, ... , Twelve members began with an olive oil tasting to whet their ...
(Date:9/20/2017)... ... September 20, 2017 , ... The award-winning producers behind ... to feature new innovations aimed at helping farmers solve the problem of nitrogen ... airs Tuesdays at 8:30aET on RFD-TV. Check your local listings for more info. ...
(Date:9/20/2017)... ... September 20, 2017 , ... Diversity focused business accelerator, The Refinery ... pitch competition to uncover the top technology-driven, women-led startups in Boston, MA, New Haven/Hamden, ... each city’s entrepreneurial events going on that week – in Boston, it will be ...
Breaking Biology Technology: