Preparation of biologically active molecules by molecular imprinting

• US 5,630,978 A
• Filed: 06/07/1995
• Issued: 05/20/1997
• Est. Priority Date: 06/07/1995
• Status: Expired due to Fees

• Current Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Original Assignee: Yissum Research Development Company of the Hebrew University of Jerusalem Ltd. (Hebrew University of Jerusalem)
• Inventors: Domb, Abraham J.
• Primary Examiner(s): KRASS, FREDERICK F
• Application Number:
  US08/476,606
• Time in Patent Office: 713 Days
• Field of Search: 526/238.1, 526/238.2, 264/330, 264/331.11, 264/331.16, 264/331.19, 424/78.08, 424/78.37
• US Class Current: 264/330
• CPC Class Codes: B01J 20/268 Polymers created by use of a template, e.g. molecularly imprinted polymers
• CPC Class Codes: C07D 207/16 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C08F 2/00 Processes of polymerisation
• CPC Class Codes: C08F 220/58 containing oxygen in addition to the carbonamido oxygen , e.g. N-methylolacrylamide, N-(meth)acryloylmorpholine
• CPC Class Codes: G01N 2600/00 Assays involving molecular imprinted polymers/polymers created around a molecular template
• CPC Class Codes: Y10S 264/44 using destructible molds or cores in molding processes

Abstract

A method for preparing mimics of a wide variety of drugs and other biologically active molecules using molecular imprinting techniques, and the mimics produced thereby, is disclosed. Specifically, the mimic is designed by: (i) polymerization of functional monomers around a known drug or biologically active molecule (the template) that exhibits a desired activity; (ii) removal of the template molecule; and then (iii) polymerization of a second class of monomers in the void left by the template, to provide a new organic molecule which exhibits one or more desired properties which are similar to that of the template.

Claims

1. A method for preparing molecules comprising:

(a) polymerization of functional monomers around a template molecule that exhibits a desired known biological activity;

(b) removal of the template molecule; and

(c) polymerization of a second class of monomers in the void left by the template.

2. The method of claim 1 wherein the resulting. molecule is a biologically active molecule.

3. The method of claim 1 wherein the template is a macromolecule.

4. The method of claim 3 where the macromolecule has a absolute molecular weight from two thousand to three million.

5. The method of claim 1 wherein the template molecule is selected from the group consisting of carbohydrates, oligosaccharides, polysaccharides, steroids, nucleic acids, nucleotides, nucleosides, oligonudeotides, genes, or vitamins.

6. The method of claim 1, wherein the template molecule is a drug.

7. The method of claim 6, wherein the drug is an immunosuppressant.

8. The method of claim 6, wherein the drug is an antioxidant.

9. The method of claim 6, wherein the drug is a chemotherapeutic agent.

10. The method of claim 6, wherein the drug is a steroid.

11. The method of claim 6, wherein the drug is a hormone.

12. The method of claim 6, wherein the drug is an antibiotic.

13. The method of claim 6, wherein the drug is an antiviral agent.

14. The method of claim 6, wherein the drug is an antifungal.

15. The method of claim 6, wherein the drug is an antiproliferative.

16. The method of claim 6, wherein the drug is an antihistamine.

17. The method of claim 6, wherein the drug is selected from the group consisting of a nonsteroidal and a steroidal anti-inflammatory compound.

18. The method of claim 1, wherein the template molecule is selected from the group consisting of insecticides, pesticides, fungicides, and rodenticides.

19. The method of claim 1, wherein the template molecule is selected from the group consisting of plant nutrients and growth promoters.

20. The method of claim 1, wherein the template molecule is a protein.

21. The method of claim 1, wherein the template is a peptide.

22. The method of claim 20, wherein the protein is selected from the group consisting of a nutrient protein, a storage protein, a contractile or motile protein, a structural protein, a defense protein, and a regulatory protein.

23. The method of claim 20, wherein the protein is selected from the group consisting of nucleoproteins, mucoproteins, lipoproteins, synthetic proteins, and glycoproteins.

24. The method of claim 1, wherein the template molecule is a small molecule linked to a protein.

25. The method of claim 11, wherein the hormone is selected from the group consisting of peptide hormones, amine hormones, steroid hormones, adrenocorticotropin, somatotropin releasing hormone, somatostatin, prolactin releasing hormone, prolactin inhibitory hormone, FSH- and LH-releasing hormone, vasopressin, and oxytocin.

26. The method of claim 1, wherein the template is a polyanion.

27. The method of claim 1, wherein the template molecule is DNA.

28. The method of claim 1, wherein the template molecule is a glycosaminoglycan.

29. The method of claim 1, wherein the template molecule is heparin.

30. The method of claim 1, wherein the template molecule is a growth factor.

31. The method of claim 1, wherein the second class of monomers comprises a vinyl monomer.

32. The method of claim 18, wherein the vinyl monomer has at least one pendent group selected from the group consisting of an amino group, amido group, carboxylic acid, sulfonic acid, phosphoric acid, and hydroxyl group.

33. The method of claim 1 wherein the polymerization of functional monomers occurs in the presence of one or more cross-linking agents, an inert solvent, and a free radical initiator.

34. The method of claim 1 wherein the second class of monomers is an alkenyl derivative of a compound selected from the group consisting of an amino acid, a carbohydrate, and a nucleoside.

35. The method of claim 1 wherein the second monomer comprises an N-acryloyl aminoacid ester.

36. The method of claim 1, wherein the second monomer comprises N-acryl-transhydroxyproline.