Navigation Links
Leeds researchers reshape the future of drug discovery
Date:11/18/2008

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.


'/>"/>

Contact: Professor Adam Nelson
a.s.nelson@leeds.ac.uk
44-011-334-36502
University of Leeds
Source:Eurekalert

Related medicine news :

1. Leeds medics solve an ancient riddle -- and offer new tool for diagnosis
2. UNC researchers find clue to stopping breast-cancer metastasis
3. U of U researchers to use patients own stem cells to treat heart failure
4. Researchers identify toehold for HIVs assault on brain
5. Researchers Tackle CLL, Diabetes and Trauma-Hemorrhage
6. Researchers Use New Method to Control Bleeding in Hemophilia
7. Stem cells with potential to regenerate injured liver tissue identified by Penn researchers
8. Protein can nurture or devastate brain cells, depending on its friends, researchers find
9. Researchers find stem cells from monkey teeth can stimulate growth and generation of brain cells
10. Battling Bacteria in the Blood: U-M Researchers Tackle Deadly Infections
11. Researchers to Present Additional Data on Soliris(R) (eculizumab) for the Treatment of PNH at the ASH Annual Meeting
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/24/2016)... Dallas, Texas (PRWEB) , ... June 24, 2016 ... ... 12th International Conference and Scientific Sessions in Dallas that it will receive two ... Announcement of the grants came as PHA marked its 25th anniversary by recognizing ...
(Date:6/24/2016)... , ... June 24, 2016 , ... ... offering micro-osteoperforation for accelerated orthodontic treatment. Dr. Cheng has extensive experience with all ... brackets , AcceleDent, and accelerated osteogenic orthodontics. , Micro-osteoperforation is a revolutionary ...
(Date:6/24/2016)... ... ... makers of Topricin and MyPainAway Pain Relief Products, join The ‘Business for a Fair Minimum ... by 2020 and then adjusting it yearly to increase at the same rate as the ... wage floor does not erode again, and make future increases more predictable. , The company ...
(Date:6/24/2016)... ... June 24, 2016 , ... EB Medicine presented its ... Emergency Medicine conference in Ponte Vedra Beach, FL. The awards honor the outstanding ... Medicine Practice and Pediatric Emergency Medicine Practice. , “With this award, we ...
(Date:6/24/2016)... Vegas, Nevada (PRWEB) , ... June 24, 2016 ... ... Las Vegas client, The Grove Investment Group (TGIG), has initiated cultivation and processing ... Grove, in Las Vegas and Pahrump, Nevada. , Puradigm is the manufacturer of ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... ALEXANDRIA, Va. , June 24, 2016 ... a set of recommendations that would allow ... information (HCEI) with entities that make formulary and coverage ... determine the "value" of new medicines. The ... that does not appear on the drug label, a ...
(Date:6/24/2016)... 24, 2016 Research and Markets has ... Companion Diagnostic Tests" report to their offering. ... Diagnostics The World Market for Companion Diagnostics ... diagnostics. Market analysis in the report includes the following: ... Vitro Diagnostic Kits) by Region (N. America, EU, ROW), 2015-2020 ...
(Date:6/24/2016)... Belgium , June 24, 2016 ... the appointment of Dr. Edward Futcher ... Non-Executive Director, effective June 23, 2016.Dr. Futcher was ... Nominations and Governance Committees.  As a non-executive member ... independent expertise and strategic counsel to VolitionRx in ...
Breaking Medicine Technology: