Molecular compounds having complementary surfaces to targets

• US 6,884,842 B2
• Filed: 10/26/2001
• Issued: 04/26/2005
• Est. Priority Date: 10/14/1997
• Status: Expired due to Fees

• Current Assignee: Alnis Biosciences, Inc.
• Original Assignee: Alnis Biosciences, Inc.
• Inventors: Goodwin, Andrew, Perrott, Michael G., Barry, Stephen E., Soane, David S., Offord, David A.
• Primary Examiner(s): Nutter, Nathan M.
• Application Number:
  US10/055,837
• Publication Number:
  US 20030153001A1
• Time in Patent Office: 1,278 Days
• Field of Search: 525/54.1, 525/54.2, 525/54.23, 526/238.1, 526/238.2, 526/238.23, 424/450, 424/489, 424/499
• US Class Current: 525/54.1
• CPC Class Codes: C08B 37/0021 Dextran, i.e. (alpha-1,4)-D-glucan; Derivatives thereof, e.g. Sephadex, i.e. crosslinked dextran
• CPC Class Codes: C08G 83/00 Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
• CPC Class Codes: G01N 2333/976 Trypsin; Chymotrypsin
• CPC Class Codes: G01N 2400/22 Dextran
• CPC Class Codes: G01N 2600/00 Assays involving molecular imprinted polymers/polymers created around a molecular template
• CPC Class Codes: G01N 33/531 Production of immunochemical test materials
• CPC Class Codes: G01N 33/68 involving proteins, peptides or amino acids involving lipoproteins G01N33/92

Abstract

Synthetic polymer complements (SPCs) are provided, as well as methods for their synthesis and use. The SPCs may have surfaces that include functional groups that are complementary to surface sites of targets such as nanostructures or macromolecular targets, and may be capable of specifically interacting with such targets. The positions of the functional groups in one embodiment are stabilized by a polymer network. The SPCs are formed by contacting the target with a set of monomers which self-assemble on the target, and then are polymerized into a network to form the synthetic polymer complement. At least a portion of the surface of the resulting SPC thus may include an imprint of the target. The complex of the SPC and the target may be the desired product. Alternatively, the target is released, for example, by controllably expanding and contracting the crosslinked network. The SPC is isolated and used in many applications.

Claims

1. A synthetic polymer complement (“

SPC”

) comprising a crosslinked three-dimensional polymeric network having a diameter less than about 1000 nm and comprising target binding sites on its surface, the target binding sites being complementary to at least a portion of the surface topology and force field of a target, and wherein the polymeric network is comprised of monomers consisting of at least one crosslinking group and at least one head group selected from the group consisting of sugars, proteins, and carbohydrates, which head group is a functional group capable of undergoing a binding interaction with a site on the target.

2. A synthetic polymer complement according to claim 1, wherein the SPC is capable of specific recognition of the target.

3. A synthetic polymer complement according to claim 1, wherein the target binding sites comprise three-dimensional cavities complementary to at least a portion of the surface topology and force field of the target.

4. A synthetic polymer complement according to claim 3, wherein the three-dimensional cavities retain their topological and force field complementarity to the target when they are not bound to the target.

5. A synthetic polymer complement according to claim 1, wherein the target is selected from the group consisting of organic compounds, toxins, pollutants, pathogens, synthetic drugs, steroids, steroid derivatives, proteins, glycoproteins, polysaccharides, lipids, lipopolysaccharides, polyanions, nucleic acid, porphyrins, substituted porphyrins, and active agents.

6. A synthetic polymer complement according to claim 1, wherein the crosslinking group is selected from the group consisting of acrylate, methacrylate, acrylamide, vinyl ether, epoxide, methacrylamide, vinylbenzene, α

-methylvinylbenzene, vinylbenzene, divinylbenzene, maleic acid derivative, diene, substituted diene, ihiol, alcohol, amine, carboxylic acid, carboxylic anhydride, carboxylic acid halide, aldehyde, ketone, isocyanate, succinimide, carboxylic acid hydrazide, glycidyl ether, sulane, siloxane, chlorosilane, alkoxysilane, alkyne, azide, 2′

-pyridyldithiol, phenylglyoxal, iodo, maleimide, aryl halides, imidoester, dibromopropionate, and iodacetyl.

7. A synthetic polymer complement according to claim 1, wherein the crosslinking group is an aclylate, a methacrylate, an acrylamide, or a methacrylamide.

8. A synthetic polymer complement according to claim 1, wherein the polymeric network is further comprised of monomers consisting of a crosslinking group without a head group.

9. A synthetic polymer complement according to claim 8, wherein the crosslinking group is an acrylate, a methacrylate, an acrylamide, or a methacrylamide.

10. A synthetic polymer complement according to claim 1, wherein the polymeric network is further comprised of monomers consisting of a crosslinking group, a head group, and a tail region.

11. A synthetic polymer complement according to claim 10, wherein the tail region comprises a moiety selected from the group consisting of a poly(ethylene glycol), poly(ethylene oxide), poly(vinyl alcohol), poly(vinylpyrrolidone), poly(ethyloxazoline), poly(ethylene oxide)-co-poly(propyleneoxide) block copolymer, polysaccharide, a poly(amino acid), and a hydrocarbon moiety.

12. A synthetic polymer complement according to claim 1, wherein the target binding sites comprise a surface having at least one functional group capable of undergoing a binding interaction with a site on a target.

13. A synthetic polymer complement according to claim 1 which comprises from 1 to about 1000 target binding sites.

14. A synthetic polymer complement according to claim 1 which comprises from 1 to 1000 binding sites and wherein the head group is a carbohydrate, the crosslinking group is acrylamide, and the target is a protein.

15. A synthetic polymer complement according to claim 1 which comprises from 1 to 1000 binding sites and wherein the monomers comprise glucose-2-acrylamide.

30. A composition comprising a synthetic polymer complement (“

SPC”

) of claim 1 in a pharmaceutically acceptable carrier.

31. A composition according to claim 30, wherein the crosslinking group of the SPC is selected from the group consisting of acrylate, methacrylate, acrylamide, vinyl ether, epoxide, methacrylamide, vinylbenzene, α

-methylvinylbenzene, vinylbenzene, divinylbenzene, maleic acid derivative, diene, substituted diene, thiol, alcohol, amine, carboxylic acid, carboxylic anhydride, carboxylic acid halide, aldehyde, ketone, isocyanate, succinimide, carboxylic acid hydrazide, glycidyl ether, silane, siloxane, chlorosilane, alkoxysilane, alkyne, azide, 2′

-pyridyldithiol, phenylglyoxal, iodo, maleimide, aryl halides, imidoester, dibromopropionate, and iodacetyl.

32. A composition according to claim 30, wherein the polymeric network of the SPC further comprises monomers consisting of a crosslinking group without a head group.

33. A composition according to claim 30, wherein the polymeric network of the SPC further comprises monomers consisting of a crosslinking group, a head group, and a tail region.

34. A composition according to claim 33, wherein the tail region comprises a moiety selected from the group consisting of a poly(ethylene glycol), poly(ethylene oxide), poly(vinyl alcohol), poly(vinylpyrrolidone), poly(ethyloxazoline), poly(ethylene oxide)-co-poly(propyleneoxide) block copolymer, polysaccharide, a poly(amino acid), and a hydrocarbon moiety.

35. A composition according to claim 30, wherein the synthetic polymer complement comprises from 1 to 1000 binding sites and wherein the head group of the monomers of the SPC is a carbohydrate, the crosslinking group is acrylamide, and the target is a protein.

36. A composition according to claim 30, wherein the synthetic polymer complement comprises from 1 to 1000 binding sites and wherein the monomers of the SPC comprise glucose-2-acrylamide.

16. A synthetic polymer complement (“

SPC”

) comprising a crosslinked three-dimensional polymeric network having a diameter less than about 1000 nm, and wherein the SPC is capable of binding a target, and wherein the SPC is formed by;

providing a set of monomers, at least some of the monomers comprising i) at least one head group, which is a functional group capable of undergoing a binding interaction with a site on the target, the head group being selected from the group consisting of sugars, proteins, and carbohydrates; and

ii) at least one crosslinking group, which is a reactive group capable of covalently reacting to crosslink monomers of the monomer set;

contacting the set of monomers with the target to permit the monomers to self assemble on the target;

reacting the crosslinking groups of the monomers of the monomer set; and

removing the target;

to form the SPC comprising one or more three-dimensional binding sites on its surface, the binding sites being complementary in shape to at least a portion of the surface of the target.

17. A synthetic polymer complement according to claim 16, wherein the crosslinking group is selected from the group consisting of acrylate, methacrylate, acrylamide, vinyl ether, epoxide, methacrylamide, vinylbenzene, α

-methylvinylbenzene, vinylbenzene, divinylbenzene, maleic acid derivative, diene, substituted diene, thiol, alcohol, amine, carboxylic acid, carboxylic anhydride, carboxylic acid halide, aldehyde, ketone, isocyanate, succinimide, carboxylic acid hydrazide, glycidyl ether, silane, siloxane, chlorosilane, alkoxysilane, alkyne, azide, 2′

-pyridyldithiol, phenylglyoxal, iodo, maleimide, aryl halides, imidoester, dibromopropionate, and iodacetyl.

18. A synthetic polymer complement according to claim 16, wherein the crosslinking group is an acrylate, a methacrylate, an acrylamide, or a methacrylamide.

19. A synthetic polymer complement according to claim 16, wherein the set of monomers further comprises monomers consisting of a crosslinking group without a head group.

20. A synthetic polymer complement according to claim 19, wherein the crosslinking group is an acrylate, a methacrylate, an acrylamide, or a methacrylamide.

21. A synthetic polymer complement according to claim 16, wherein the set of monomers further comprises monomers consisting of a crosslinking group, a head group, and a tail region.

22. A synthetic polymer complement according to claim 21, wherein the tail region comprises a moiety selected from the group consisting of a poly(ethylene glycol), poly(ethylene oxide) poly(vinyl alcohol), poly(vinylpyrrolidone), poly(ethyloxazoline), poly(ethylene oxide)-co-poly(propyleneoxide) block copolymer, polysaccharide, a poly(amino acid), and a hydrocarbon moiety.

23. A synthetic polymer complement according to claim 16, wherein the set of monomers further comprises a non-ionic surfactant.

24. A synthetic polymer complement according to claim 16, wherein at least some of the monomers are amphiphilic.

25. A synthetic polymer complement according to claim 16, wherein at least some of the monomers comprise a carbohydrate moiety.

26. A synthetic polymer complement according to claim 16, wherein at least some of the monomers comprise styrene, divinylbenzene or vinylbenzoic acid, and wherein the set of monomers further comprises a non-ionic surfactant.

27. A synthetic polymer complement according to claim 16 which comprises from 1 to about 1000 target binding sites.

28. A synthetic polymer complement according to claim 16 which comprises from 1 to 1000 binding sites and wherein the head group is a carbohydrate, the crosslinking group is acrylamide, and the target is a protein.

29. A synthetic polymer complement according to claim 16 which comprises from 1 to 1000 binding sites and wherein the set of monomers comprises glucose-2-acrylamide.