Hydrogel based Molecularly Imprinted Polymers (HydroMIPs)

Description:

Summary

Improved growth of protein crystals using molecularly imprinted polymers.

Scientists from the University of Surrey and Imperial College London have come up with an invention which uses hydrogel based molecularly imprinted polymers (HydroMIPs) for protein crystallization, providing a higher yield of protein crystals over current techniques. This method also works with protein structures that are difficult to crystallise using other methods.

MIPs are polymers which are formed in the presence of a molecule which once extracted leaves behind complamentary cavities. These allow highly selective rebinding of the original molecule.

Obtaining useful crystals remains a problem in proteomics and structural biology. Previously identified nucleants with desirable properties for the task fall down because they have no specificity for individual proteins however our novel technique takes this difficulty away as the MIPs are designed specifically to attract a template protein.

Benefits

  • MIPs act as effective nucleants for the formation of large single crystals of otherwise hard to crystallize proteins
  • Improved accuracy in screening experiments leading to successful hits missed by other types of nucleant

Applications

  • Protein Crystallization
  • Protein purification/isolation
  • Replacement of biological antibodies in immunoassays
  • Catalysis
  • Biosensors for medicine, food and the environment

Availability

Available for licensing/developmental partnership

IP status

Patent Pending

 

Technical

In the paper "Protein crystallization facilitated by molecularly imprinted polymers" (published in PNAS) seven proteins were tested by imprinting them in MIPS. These were lysozyme, trypsin, catalase, haemoglobin, intracellular xylanase IXT6-R217W, alphas crustacyanin and human macrophage migration inhibitory factor.  All with the exception of catalase were able to induce the formation of crystals of nine tested proteins. This included some non-cognate proteins with similar molecular weight.

One of the crystals grown was that of HIV protein with a diffraction of 4.2Å. Other techniques that have tried to crystallize this complex have failed and have produced crystals with diffraction beyond 9Å.

When the experiments were repeated under the same conditions using other known nucleants e.g. human hair, zeolites etc. Only lysozyme and trypsin generated crystals and these were small multiple crystals compared to the large single crystals produced using MIPs.

The hit rate index screens for certain proteins showed four of five hits when the cognate MIPs were present and no hits when they were not. The results show that in the presence of MIPS, 8 to 10% of the screening trials of the target proteins produced hits that would.

Patent Information:
Category(s):
Chemistry
For Information, Contact:
Will Lovegrove
University of Surrey
w.lovegrove@surrey.ac.uk
Inventors:
Keywords:
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