Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Leeds researchers reshape the future of drug discovery

19.11.2008
Scientists in Leeds have devised a new way to create the next generation of man-made molecules in a breakthrough that could revolutionise drug development.

Creating new drugs to combat disease and illness requires the completion of a complex 3D jigsaw. The shape of the drug must be right to allow it to bind to a specific disease-related protein and to work effectively, and this shape is determined by the core framework of the molecule.

Now a team from the Astbury Centre for Structural Molecular Biology at the University of Leeds has developed a new approach which allows the creation of molecules with an extraordinarily wide range of molecular frameworks and, hence, shapes. The new molecules are likely to have a wide range of biological functions, which means they could be valuable starting points for the discovery of new drugs.

Says lead researcher Professor Adam Nelson of the University’s School of Chemistry: “Nature has created hundreds of thousands of molecules that have different frameworks and biological purposes, but in the global pursuit of new drugs, chemists from around the world are racing to create new molecules with functions not seen in nature.”

The newly created molecules are being shared with colleagues in the Faculties of Biological Sciences and Medicine and Health to see if specific new molecular frameworks match the requirements of their own research.

Of the 30 million or so synthetic molecules made throughout the history of organic chemistry, many are based on an extremely small number of core frameworks, with the main differences being the groups attached at the periphery. “Making collections of similar molecules is great for optimising a biological property,” says Professor Nelson, “but to put it simply, if researchers need a cube-shaped molecule to target a particular protein, they may well find that they can only choose from libraries stocked with millions of sphere-shaped ones.”

Co-researcher Dr Stuart Warriner added: “Making molecules is a bit like making something using lego bricks. Up until now we’ve only really become good at making, say, the equivalent of a lego car or train. There might be 30 million synthetic molecules registered, but there’s probably several million of these that are the equivalent of lego cars – they may have different wheels and wing mirrors, but their fundamental shape is essentially the same. We’ve not really scratched the surface of the possible structures that could be made. This lack of variety in the core shape of molecules may well limit the range of proteins that medicinal chemists can target.”

The Leeds approach makes use of ‘metathesis’, a reaction that won the 2005 Nobel Prize in Chemistry.

Explains Professor Nelson: “We take simple building blocks, a bit like the amino acids that make up peptides, and we assemble them in different sequences using three simple reactions to link them together in a chain. The key difference is that we then add the catalyst which initiates a ‘scaffold reprogramming reaction’, which ripples down the chemical chain and restitches the molecule together in a completely different way each time.

“It’s a bit like a molecular square dance, where atoms in the molecule swap partners - and the exciting thing is that we can change the building blocks again and again in different combinations as a really powerful way to vary the core frameworks that result. The potential of this process is enormous,” he says.

The team from Leeds have used their approach to prepare molecules with 84 distinct molecular frameworks – and about two-thirds of the frameworks are unprecedented in the history of organic chemistry. The work is a huge leap forward from landmark research reported in 2003, which resulted in the creation of six frameworks in a single process. It is also a significant improvement on more recent research in which around 30 frameworks were created using a complex combination of different reactions.

The team has deliberately chosen to prepare molecules with structural features that are similar to those found in natural products: “For example we know that putting oxygen atoms on every other carbon atom is something that frequently occurs in nature and has evolved for a useful purpose” says Professor Nelson. “We’re not aiming to improve on existing natural products or drugs - we want to create molecules with functions that nature’s not got round to making yet, or something that would only evolve naturally with new selection pressures that would make it beneficial for the organism.”

Work has already begun across campus to screen the molecules, which are already yielding “promising” results. The team are considering patenting molecules with novel biological functions.

The research is funded both through Professor Nelson’s Engineering and Physical Sciences Research Council (EPSRC) Advanced Research Fellowship and by the Wellcome Trust.

The research, published online today, has earned the paper VIP status in the leading Chemistry journal Angewandte Chemie.

Jo Kelly | alfa
Further information:
http://www.leeds.ac.uk

More articles from Life Sciences:

nachricht Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg

nachricht Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

A Keen Sense for Molecules

23.02.2018 | Physics and Astronomy

“Laser Technology Live” at the AKL’18 International Laser Technology Congress in Aachen

23.02.2018 | Trade Fair News

Newly designed molecule binds nitrogen

23.02.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>