Molecularly imprinted polymer

Abstract

To facilitate preparation of a molecularly imprinted polymer (MIP) which specifically binds a particular template substance, a virtual library of functional monomers is screened to find those that interact strongly with a molecular model of the substance. A selected few are then “annealed” with the substance in a computer simulation. This shows the optimum ratios of template substance to individual monomers. An appropriate mixture of monomers is then polymerised in the presence of the template to produce a MIP.

1 . A method of preparing a molecularly imprinted polymer which is adapted to interact with a template substance, the method comprising the steps of: 
 (a) producing a virtual library of molecular models of functional monomers having polymerisable portions and binding portions capable of reversibly binding to a template substance;    (b) providing a molecular model of the template substance;    (c) screening the virtual library with the molecular model of the template substance and determining a plurality of the monomers found to bind strongly to it;    (d) providing a chemical reaction system containing said plurality of monomers and said template substance and effecting polymerisation of said monomers to produce a molecularly imprinted polymer.    
     
     
         2 . A method according to  claim 1  wherein said screening step (c) involves (c-i) calculating interaction energies between individual monomers and the template substance to identify a plurality of said monomers able to bind relatively strongly to the template substance; and (c-ii) using molecular mechanical calculations to estimate how said plurality of monomers would bind to said template substance, thereby determining optimum ratios of template substance to monomers; and wherein said step (d) employs a reaction system containing amounts of template substance and monomers in accordance with said ratios.  
     
     
         3 . A process according to  claim 1  or  claim 2  wherein said functional monomers in said virtual library comprise one or more of vinyl monomers, allyl monomers, acetylenes, acrylates, methacrylates, amino acids, nucleosides, nucleotides, carbohydrates, phenols, heterocycles, aniline, and their derivatives.  
     
     
         4 . A process according to  claim 1 ,  2  or  3  wherein said template substance is selected from biological receptors, nucleic acids, immunosuppressants, hormones, heparin, antibiotics, vitamins, drugs or synthetic molecules possessing biological activity, cell components and components of viruses such as carbohydrates, lipids, saccharides, nucleoproteins, mucoproteins, lipoproteins, peptides and proteins, glycoproteins, glucosaminoglycanes and steroids.  
     
     
         5 . A polymer as produced by the process of any preceding claim.  
     
     
         6 . Use of a polymer as produced by the process of any of claims  1 - 4  for selectively binding the template substance or a related compound.  
     
     
         7 . A procedure of computer aided rational design techniques for the rapid development and optimization of molecularly imprinted polymers (MIPs) which includes screening of a virtual library of functional monomers for their interaction with a template molecule and selection of those monomers giving a strong complex with the template for polymer preparation.  
     
     
         8 . The procedure of  claim 7  wherein the template is selected from biological receptors, nucleic acids, immunosuppressants, hormones, heparin, antibiotics, vitamins, drugs or synthetic molecules possessing biological activity, cell components and components of viruses such as carbohydrates, lipids, saccharides, nucleoproteins, mucoproteins, lipoproteins, peptides and proteins, glycoproteins, glucosaminoglycanes and steroids.  
     
     
         9 . A computer-aided rational design technique for the rapid development and optimization of MIPs which comprises placing functional monomers around a template and using molecular mechanics to simulate, pre-arrangement of the functional monomers with template in the monomer mixture.  
     
     
         10 . Computer-aided rational design technique for the rapid development and optimization of molecularly imprinted polymers which includes two steps: first, screening of a virtual library of functional monomers for their interaction with a template molecule; second, selection of those monomers which form a strong complex with the template for use in a refining step, when two or more functional monomers are placed around the template and molecular mechanics is used to simulate pre-arrangement of the functional monomers with template in the monomer mixture.  
     
     
         11 . A computer-aided rational design technique for the rapid development and optimization of molecularly imprinted polymers as described in  claim 7 ,  claim 9  or  claim 10  where parameters of the modeling and screening suitably comprising one or more of dielectric constants, temperature chosen for “annealing” procedure, and type of interactions, are adjusted according to the real polymerization or re-binding conditions.  
     
     
         12 . A virtual library of functional monomers for use in the procedure of any of claims  7 - 11  containing at least two monomers which possess polymerizable residues and residues able to interact with a template through one or more of electrostatic, hydrophobic, van-der-Waals forces, dipole-dipole interactions and reversible covalent bonds, the monomers being selected from vinyl monomers, allyl monomers, acetylenes, acrylates, methacrylates, amino acids, nucleosides, nucleotides, carbohydrates, phenols, heterocycles, aniline, and their derivatives.