Scientists hoping to discover new drugs have found a way to study proteins from the body using polymer templates of the molecules.
A team from Imperial College London and Surrey University is using molecularly imprinted polymers (MIP) to create crystal forms of proteins that regulate functions in the body.
This makes the proteins easier to study using X-rays and so could help researchers find new ways to target the molecules with drugs.
MIPs are compounds made up of small units that bind together around the outside of a molecule. When the molecule is extracted, it leaves a cavity that retains its shape and has a strong affinity for the target molecule.
This property makes MIPs ideal nucleants – substances that bind protein molecules and make it easier for them to come together to form crystals – especially as they can be designed specifically to attract a particular protein, something not done before.
‘Proteins are very comfortable in solution. They need some convincing to come out and form a crystal,’ said research leader Professor Naomi Chayen from Imperial’s department of surgery and cancer.
‘MIPs help this process by using the protein as a template for forming its own crystal. Once the first molecule or group of molecules is held in place, other molecules can arrange themselves around it and start to build a crystal.’
Once a protein is crystallised, a technique called X-ray crystallography can be used to analyse the arrangement of its atoms. Scientists can then design a drug molecule to interact with the protein to stimulate or block its function.
Current methods of crystallisation have only allowed researchers to study less than 20 per cent of relevant identified proteins.
‘Rational drug design depends on knowing the structure of the protein you’re trying to target, and getting good crystals is essential for studying the structure,’ Professor Chayen said.
‘With MIPs we can get better crystals than we can with other methods, and also improve the probability of getting crystals from new proteins.
‘This is a really significant innovation that could have a major impact on research leading to the development of new drugs.’
In a study published in the Proceedings of the National Academy of Science, Professor Chayen’s team found that six different MIPs induced crystallisation of nine proteins in conditions that do not otherwise give crystals.
MIPS were also successful in yielding crystals in eight to 10 per cent of tests of three target proteins for which scientists have previously been unable to obtain crystals of sufficient quality.
The research was funded by the Engineering and Physical Sciences Research Council (EPSRC) and the European Commission.