CREATION OF MIPS
Project Information AT A GLANCE
Project Title: Smart Materials: Development of Protein Recognition Polymers as Novel Surfaces for Protein Crystallization.
Project Objective: To investigate a new idea of designing molecularly imprinted polymers as triggers for forming protein crystals which are vital for facilitating rational drug design.
Project Duration and Timing: 18 Months
Project Funding: Engineering and Physical Sciences Research Council (EPSRC) grant numbers EP/G014736/1 and EP/ G014299/1
is extracted, it leaves a cavity that retains its shape and has a strong affinity for the target molecule. This property interested Chayen enough for her to investigate the MIPs further. She contacted Dr Sub Reddy at the University of Surrey, who had been developing protein-based molecularly imprinted polymers for the development of novel protein diagnostics. Dr Reddy made ‘personalised’ MIPs for her with cavities that would pull their own protein molecules back, creating the perfect environment for the subsequent crystallization process. “MIPs help the crystallization process
by using the protein as a template for forming its own crystal,” explains Chayen. “Once the first small group of molecules is held in place, other molecules can arrange themselves around it and start to build a crystal.” Chayen’s team, in particular Dr Emmanuel
Saridakis, Dr Sahir Khurshid and Dr Lata Govada, then demonstrated that MIPs are effective in both the screening and optimisation stages of crystallization. MIP- containing screening trials (in a widely used commercial screen) yielded promising hits for three proteins that had not produced useful crystals before. No hits were obtained in the absence of MIPs or in the presence of traditional nucleants, meaning that without MIPs these important hits would have been missed. An additional key discovery was that
better crystals could be obtained in the presence of MIPs at the optimisation stage. Nine proteins out of ten tested produced
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higher quality crystals (as measured by X-ray diffraction), notably of
an HIV
protein complex. The findings went beyond the team’s
expectations. “When embarking on the MIP experiments, we expected that each MIP would work exclusively on its cognate protein and that it would be necessary to make a MIP for each protein to be crystallised,” says Chayen. “In practice, our results showed that a MIP imprinted with one protein could also be successfully used for other size-compatible proteins. This is very important in the case of difficult to crystallise proteins, which are usually too scarce in supply for imprinting and would therefore benefit from the use of a related MIP made from a cheap and abundant protein.” The results were published in PNAS in
July 2011 (vol. 108, 11081-11086) and the paper is receiving ongoing coverage: e.g. Research News Highlight in Nature Methods, News and Views in Nature Chemistry, New Scientist (under cutting- edge science) and by numerous other sites, as well as by the London Press Service. A patent application has been filed and is at the PCT stage. These new breakthroughs are ushering in
an exciting new era for drug research. By using MIPs, Professor Chayen and her colleagues‘ work will enable more proteins to crystallise than ever before as well as to increase the quality of the crystals. This significant innovation has the potential to have a major impact on research leading to the development of new drugs.
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Project Partners: Dr S.M. Reddy, University of Surrey
Main Contact:
Professor Naomi Chayen Naomi E. Chayen is Professor of Biomedical Sciences at Imperial College London. She specializes in the crystallization of proteins, developing unique methods adopted by laboratories worldwide, several of which are commercialised (e.g. ‘Naomi’s Nucleant’). She is recipient of Innovator of the Year (2011) Prize and Women of Outstanding Achievement for Innovation and Entrepreneurship Commendation (2012) presented by the Princess Royal.
Contact: Tel: +44 207 594 3240 Email:
n.chayen@
imperial.ac.uk Web:
www.imperial.ac.uk/medicine/ people/
n.chayen/
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