Preparation and application of artificial anti-idiotypic imprints

• US 6,489,418 B1
• Filed: 04/02/1996
• Issued: 12/03/2002
• Est. Priority Date: 02/10/1994
• Status: Expired due to Fees

• Current Assignee: Klaus Mosbach
• Original Assignee: Klaus Mosbach
• Inventors: Mosbach, Klaus
• Primary Examiner(s): KRASS, FREDERICK F
• Application Number:
  US08/626,342
• Time in Patent Office: 2,436 Days
• Field of Search: 264/108, 264/219, 264/220, 264/221, 264/225, 264/226, 264/227, 264/330, 264/DIG.44, 264/330.11, 264/331.16, 264/331.19, 424/78.08, 424/78.37, 526/238.1, 526/238.2, 435/183, 435/188.5, 530/387.1, 530/388.1, 530/388.9, 530/389.8
• US Class Current: 526/238.1
• CPC Class Codes: B01J 20/268 Polymers created by use of a template, e.g. molecularly imprinted polymers
• CPC Class Codes: C07K 16/4208 against an idiotypic determinant on Ig
• CPC Class Codes: G01N 2600/00 Assays involving molecular imprinted polymers/polymers created around a molecular template
• CPC Class Codes: G01N 33/686 Anti-idiotype
• CPC Class Codes: Y10S 264/44 using destructible molds or cores in molding processes

Abstract

This patent application describes the use of molecular imprinting as a means for preparation of anti-idiotypic imprint matrices. With this technique, imprints of artificial or natural molecules including their recognition sites, such as of molecularly imprinted polymers or biological receptors, antibodies or enzymes, can be prepared. In the former case, using the original imprints as casts or molds in a subsequent polymerisation step, utilising preferentially functionally complementary monomers, the formation of imprint materials containing recognition sites complementary in shape and functionality with the original imprint can be obtained but being of different composition. Alternatively, imprints or images of the artificial or biological species can be obtained directly. The so formed preparations can be used in a vast variety of applications, e.g. as new drugs, inhibitors or new affinity materials.

Claims

1. A method of producing a molecular imprint of an artificial or native molecule, comprising the following steps:

(1) polymerizing a mixture comprising monomers and crosslinkers in the presence of a molecule for which a molecular imprint is to be produced, thereby forming a matrix comprising an imprint of the molecule;

(2) separating the molecule from the matrix;

(3) polymerizing in a subsequent step a mixture of monomers and crosslinkers which are the same or different from the monomers and crosslinkers utilized in the first polymerization step, wherein polymerization is conducted in the imprint in the matrix, thereby creating a molecular imprint of the molecule, which molecular imprint possesses the same functionality and/or shape as said molecule; and

(4) separating the resultant molecular imprint from the imprint in the matrix.

4. The method according to claim 1, wherein the artificial or native molecule used to produce the molecular imprint is selected from the group consisting of compounds having moieties comprising artificial or natural binding sites.

5. The method according to claim 4, wherein said compounds having moieties comprising artificial or natural binding sites are selected from the group consisting of nucleotides, receptors, antibodies, enzymes, catalysts and molecular imprints of said compounds.

15. The method according to claim 1 or 2, wherein the molecular imprint produced is selected from the group consisting of inhibitors, drugs, affinity ligands, anti-affinity materials, anti-antibodies, nucleotides, antigens, enzymes and catalysts.

16. The method according to claim 15, wherein said anti-affinity material is a cell-affinity material.

19. The method of claim 1 or 17, where in step (4) the molecular imprint is separated from the imprint in the matrix by dissolution of said matrix.

20. The method of claim 1 or 17, where in step (2) the molecule is separated from the matrix by dissolution of the matrix.

21. The method of claim 1 or 17, wherein the imprint molecule is comprised of a magnetic bead and the imprint molecule is separated from the matrix in step (2) by application of a magnetic field.

22. The method of claim 1 or 17, wherein the molecule that is imprinted is a protease inhibitor.

23. The method of claim 1 or 17, wherein the molecule that is imprinted is acetylcholine.

2. A method of producing a molecular imprint of surface bound artificial or native molecules comprising the following steps:

(1) polymerizing a mixture of monomers and crosslinkers resulting in the formation of a film having imprints of the surface bound molecules;

(2) separating the imprinted film from the surface bound molecules;

(3) polymerizing a second mixture of monomers and crosslinkers which are the same or different from the monomers and crosslinkers utilized in the first polymerization step on the imprinted film, thereby producing a molecular imprint of the surface bound molecules which possesses the same functionality and/or shape as the surface bound molecules; and

(4) removing the resultant molecularly imprinted film from the imprinted film.

6. The method according to claim 2, wherein the artificial or native molecule used to produce the molecular imprint is selected from the group consisting of compounds having moieties comprising artificial or natural binding sites.

7. The method according to claim 6, wherein said compounds having moieties comprising artificial or natural binding sites are selected from the group consisting of nucleotides, receptors, antibodies, enzymes, catalysts and molecular imprints of said compounds.

18. The method according to claim 7, wherein said anti-affinity material produced by said method is a cell-affinity material.

24. The method of claim 2 or 3, wherein the film is produced on a microslide.

3. A method of producing a molecular imprint of surface bound artificial or native molecules comprising the following steps:

(1) polymerizing a mixture of monomers and crosslinkers by a method which results in the formation of a film having molecular imprints of surface bound molecules; and

(2) separating the resulting molecularly imprinted film from the surface bound molecules.

8. The method according to claim 3, wherein the artificial or native molecule used to produce the molecular imprint is selected from the group consisting of compounds having moieties comprising artificial or natural binding sites.

9. The method according to claim 8, wherein said compounds having moieties comprising artificial or natural binding sites are selected from the group consisting of nucleotides, receptors, antibodies, enzymes, catalysts and molecular imprints of said compounds.

10. A method for producing an anti-idiotypic molecular imprint of a molecule having artificial or natural binding sites comprising polymerizing a mixture of monomers and crosslinkers within the cavities produced by the molecular imprinting of molecules possessing artificial or natural binding sites, wherein the monomers and crosslinkers become oriented within said binding sites prior to polymerization thereby forming, upon polymerization, a compound which is an anti-idiotype of the original imprint molecule.

11. The method of claim 10, wherein the monomers are selected from the group consisting of acrylic monomers, silanes and azides.

12. A method for the production of anti-idiotypic compounds which are molecular imprints of artificial or native molecules which comprises forming, by the polymerization of monomers and crosslinkers, a molecular imprint of a previously synthesized molecular imprint.

13. The method according to claim 12, wherein the molecular imprints of the artificial or native molecules are selected from the group consisting of inhibitors, drugs, affinity ligands, antibodies, enzymes, catalysts, nucleotides and receptors.

14. A method for the production of an anti-idiotypic molecular imprint, comprising forming, by the polymerization of monomers and crosslinkers, chiral cavities from non-chiral basic compounds or chiral monomers, thereby forming said anti-idiotypic molecular imprint.

17. A molecular imprinting method which results in the formation of a molecule selected from the group consisting of inhibitors, drugs, affinity ligands, antibodies, anti-affinity materials, nucleotides, antigens, enzymes and catalysts, which method comprises the following steps:

(1) producing a molecular imprint by polymerizing monomers and crosslinkers in the presence of a molecule selected from the group consisting of inhibitors, drugs, affinity ligands, antibodies, anti-affinity materials, nucleotides, antigens, enzymes and catalysts, thereby producing a matrix comprising an imprint of the molecule;

(2) separating the molecule from the matrix;

(3) polymerizing in a subsequent step a mixture of monomers and crosslinkers which are the same or different from the monomers and crosslinkers utilized in the first polymerization step, wherein polymerization is conducted in the imprint in the matrix, thereby creating a molecular imprint of the molecule, which molecular imprint possesses the same functionality and/or shape as said molecule; and

(4) separating the resultant molecular imprint from the imprint in the matrix, thereby producing a molecular imprint which is a compound selected from the group consisting of inhibitors, drugs, affinity ligands, antibodies, anti-affinity materials, nucleotides, antigens, enzymes and catalysts.