Claims
- 1. A synthetic receptor which comprises a polyfunctional organic template covalently linked to two or more oligomers which may independently be the same or different and may independently be straight chain, cyclic or branched.
- 2. The synthetic receptor of claim 1, wherein the polyfunctional organic template is an acyclic, a carbocyclic, a heterocycle, a polycarbocycle, a polycyclic hydrocarbon, a polyheterocycle, a macrocyclic polyether, a macrocyclic polyamine, a macrocyclic polyamide, macrocyclic polyester, a macrobicycle, a macrotricycle, a macrotetracycle, a podand or
- 3. The synthetic receptor of claim 2, wherein the polyfunctional organic template is
- 4. The synthetic receptor of claim 1, wherein each oligomer contains less than ten monomers.
- 5. The synthetic receptor of claim 1, wherein at least one of the oligomers is an oligoamide, an oligoester, an oligourea, an oligourethane, an oligoamine, an oligoether, an oligosulfonamide, an oligophosphonamide, an oligophosphonate, an oligophosphate, an oligonucleotide, an oligosaccharide, a peptide oligomer, a cyclophane or a mixture of monomers thereof.
- 6. The synthetic receptor of claim 1, wherein at least one of the oligomers is a combination of two or more distinct classes of oligomers selected from the group consisting of an oligoamide, an oligoester, an oligourea, an oligourethane, an oligoamine, an oligoether, an oligosulfonamide, an oligophosphonamide, an oligophosphonate, an oligophosphate, an oligonucleotide, an oligosaccharide, a cyclophane or a peptide oligomer.
- 7. The synthetic receptor of claim 1, wherein the oligomers are different.
- 8. The synthetic receptor of claim 1, wherein the oligomers are the same.
- 9. A synthetic receptor which comprises a polyfunctional steroid template covalently linked to two or more peptide oligomers which may independently be the same or different and which may independently be straight chain, cyclic or branched.
- 10. The synthetic receptor of claim 9, wherein the polyfunctional steroid template is ursodeoxycholic acid, hyodeoxycholic acid. alpha-apocholic acid,
- 11. The synthetic receptor of claim 9, wherein the peptide oligomer comprises at least two amino acids.
- 12. The synthetic receptor of claim 1, wherein the polyfunctional organic template is further linked to a dye, a fluorescent label or a radioactive label.
- 13. The synthetic receptor of claim 1, wherein the polyfunctional organic template is further linked to an identifier which uniquely defines the synthetic receptor.
- 14. The synthetic receptor of claim 13, wherein the identifier uniquely defines the synthesis and molecular structure of the oligomers of the synthetic receptor.
- 15. The synthetic receptor of claim 13, wherein the identifier is a stable chemical molecule or a plurality of stable chemical molecules distinguishable and detectable to picomolar levels.
- 16. The synthetic receptor of claim 13, wherein the identifier is an oligonucleotide.
- 17. A synthetic receptor which comprises a polyfunctional organic template covalently linked to a solid support and to two or more oligomers which may independently be the same or different and which may independently be straight chain, cyclic or branched.
- 18. The synthetic receptor of claim 17, wherein the solid support is a particle composed of cellulose, controlled-pore glass, silica gel, polystyrene, PEG-polystyrene, polystyrene optionally cross-linked with divinylbenzene, grafted co-poly, poly-acrylamide, latex, polydimethylacrylamide optionally cross-linked with N,N′-bis-acryloyl ethylene diamine, glass coated with a polymer, or low molecular weight non-cross-linked polystyrene and wherein the particle is a spheroid, a capillary, a hollow fiber, a needle, or a solid fiber.
- 19. The synthetic receptor of claim 9, wherein the polyfunctional steroid template is covalently linked to a solid support.
- 20. The synthetic receptor of claim 19, wherein the solid support is polystyrene or PEG-polystyrene particles.
- 21. The synthetic receptor of claim 17, wherein the solid support is further linked to an identifier which uniquely identifies the synthetic receptor covalently linked to the solid support.
- 22. The synthetic receptor of claim 21, wherein the identifier uniquely defines the synthesis and molecular structure of the oligomers of the synthetic receptor.
- 23. The synthetic receptor of claim 21, wherein the identifier is a stable chemical molecule or a plurality of stable chemical molecules distinguishable and detectable to picomolar levels.
- 24. The synthetic receptor of claim 21, wherein the identifier is an oligonucleotide.
- 25. A library comprising a plurality of distinct synthetic receptors, wherein each synthetic receptor comprises a polyfunctional organic template covalently linked to two or more oligomers which may independently be the same or different and which may independently be straight chain, cyclic or branched.
- 26. The library of claim 25, wherein the library comprises at least 100 distinct synthetic receptors.
- 27. The library of claim 25, wherein the library comprises at least 103 distinct synthetic receptors and preferably 106 or 109 distinct synthetic receptor members.
- 28. The library of claim 25, wherein the synthetic receptors are covalently linked to a solid support.
- 29. The library of claim 28, wherein there are at least 100 unique solid supports.
- 30. The library of claim 25, wherein the solid support is linked to an identifier or identifiers which uniquely define the synthetic receptors.
- 31. The library of claim 25, wherein the polyfunctional organic template is further linked to an identifier or identifiers which uniquely define the synthetic receptors.
- 32. The library of claim 30, wherein the identifier is a stable chemical molecule or a plurality of stable chemical molecules distinguishable and detectable to picomolar levels.
- 33. The library of claim 30, wherein the identifier is an oligonucleotide.
- 34. The library of claim 31, wherein the identifier is a stable chemical molecule or a plurality of stable chemical molecules distinguishable and detectable to picomolar levels.
- 35. The library of claim 31, wherein the identifier is an oligonucleotide.
- 36. A method of preparing a synthetic receptor library with identifiers comprising a plurality of different synthetic receptor members, wherein each synthetic receptor library member comprising a solid support having attached a single type of synthetic receptor which comprises a polyfunctional organic template covalently linked to two or more oligomers which may be independently the same or different and which may independently be straight chain, cyclic or branched and one or more identifiers which define the synthetic receptor, the method comprising the steps of:
a) reacting the solid supports in a reaction vessel with a polyfunctional organic template; b) apportioning the solid supports with the attached polyfunctional organic template among a plurality of reaction vessels; c) reacting the polyfunctional organic template on a solid support in each reaction vessel with a first oligomer monomer; d) reacting the solid supports in each reaction vessel with a first identifier; e) pooling the solid supports; f) apportioning the pooled supports among a plurality of reaction vessels; g) reacting the polyfunctional organic template on solid support in each reaction vessel with a second oligomer monomer; h) reacting the pooled solid supports in each reaction vessel with a second identifier; and i) repeating steps (e) through (h) from at least one to twenty times for each oligomer of the synthetic receptor.
- 37. A method of preparing a synthetic receptor with one or more identifiers which comprises a polyfunctional organic template covalently linked to two or more oligomers which may independently be the same or different and which may independently be straight chain, cyclic or branched and one or more identifiers attached to the solid support which define the molecular structure of the oligomers of the synthetic receptor, the method comprising the steps of:
a) preparing a bifunctional solid support containing a first type of active site blocked with a first type of protecting group and a second type of active site blocked with a second type of protecting group; b) reacting the solid support with an activator to remove the first type of protecting group thereby exposing the first type of active site; c) coupling a protected polyfunctional organic template to the first type of active site; d) reacting the protected polyfunctional organic template with an activator to remove the first type of protecting group thereby exposing the first type of active site; e) coupling a protected oligomer monomer to the deprotected polyfunctional organic template; f) reacting the solid support with an activator to remove the second type of protecting group thereby exposing the second type of active site; g) coupling a protected identifier to the second type of active site; and h) repeating steps (d) through (g) from one to twenty times for each oligomer of the synthetic receptor.
- 38. A method of preparing a synthetic receptor with one or more identifiers which comprises a polyfunctional organic template covalently linked to two or more oligomers which may independently be the same or different and which may independently be straight chain, cyclic or branched and one or more identifiers attached to the solid support which define the molecular structure of the oligomers of the synthetic receptor, the method comprising the steps of:
a) coupling a protected polyfunctional organic template to a solid support; b) reacting the protected polyfunctional organic template with an activator to remove the protecting group thereby exposing the active site; c) coupling a protected oligomer monomer to the deprotected polyfunctional organic template; d) coupling an identifier to the solid support; and e) repeating steps (b) through (d) from one to twenty times for each oligomer of the synthetic receptor.
- 39. A method of preparing a synthetic receptor library with identifiers comprising a plurality of different synthetic receptor members, wherein each synthetic receptor library member comprising a solid support having attached a single type of synthetic receptor which comprises a polyfunctional organic template covalently linked to two or more oligomers which may be independently the same or different and which may independently be straight chain, cyclic or branched and one or more identifiers which define the synthetic receptor, the method comprising the steps of:
a) apportioning the solid supports among a plurality of reaction vessels; b) reacting the solid supports in each reaction vessel with a first oligomer monomer; c) reacting the solid supports in each reaction vessel with a first identifier; d) pooling the solid supports; e) apportioning the pooled supports among a plurality of reaction vessels; f) reacting solid supports in each reaction vessel with a second oligomer monomer; g) reacting the pooled solid supports in each reaction vessel with a second identifier; h) repeating steps (d) through (g) from at least one to twenty times for each oligomer; and i) reacting the solid supports in each reaction vessel with a polyfunctional organic template.
- 40. A method of preparing a synthetic receptor with one or more identifiers which comprises a polyfunctional organic template covalently linked to two or more oligomers which may independently be the same or different and which may independently be straight chain, cyclic or branched and one or more identifiers attached to the solid support which define the molecular structure of the oligomers of the synthetic receptor, the method comprising the steps of:
a) prepare a multifunctional solid support containing a active sites blocked with protecting groups; b) reacting the solid support with an activator to remove a first type of protecting group thereby exposing a first type of active site; c) coupling a protected oligomer monomer to the first type of active site of the solid support; d) react the solid support with an activator to remove a second type of protecting group thereby exposing a second type of active site; e) coupling a protected identifier to the second type of active site; and f) repeating steps (b) through (e) from one to twenty times for each oligomer; g) reacting the protected oligomer on the solid support with an activator to remove the protecting group thereby exposing an active site; h) coupling a polyfunctional organic template to the active site.
- 41. A method of preparing a synthetic receptor with one or more identifiers which comprises a polyfunctional organic template covalently linked to two or more oligomers which may independently be the same or different and which may independently be straight chain, cyclic or branched and one or more identifiers attached to the solid support which define the molecular structure of the oligomers of the synthetic receptor, the method comprising the steps of:
a) coupling a protected oligomer monomer to the solid support; b) coupling an identifier to the solid support; c) repeating steps (a) and (b) from one to twenty times for each oligomer; d) reacting the protected oligomers on the solid support with an activator to remove the protecting group thereby exposing the active site; and e) coupling a polyfunctional organic template to a oligomers.
- 42. The method of claim 36, 37, 38, 39, 40 or 41, wherein the identifier is a stable chemical molecule or a plurality of stable chemical molecules distinguishable and detectable to picomolar levels.
- 43. The method of claim 36, 37, 38, or 39, wherein the identifier is an oligonucleotide.
- 44. The method of claim 36, 37, 38, 39, 40, or 41, wherein the solid supports coupled to the polyfunctional organic templates in each reaction vessel are first reacted with an identifier and then the polyfunctional organic templates on the solid supports are reacted with an oligomer monomer.
- 45. A method for assaying a synthetic receptor library to determine a suitable synthetic receptor for an acceptor molecule of interest, the method comprising the steps:
a) generating the synthetic receptor library of claim 25;b) contacting the synthetic receptor library with the acceptor molecule of interest under conditions such that the acceptor molecule interacts and binds to one or more suitable synthetic receptors of the synthetic receptor library; c) isolating the suitable synthetic receptor(s) that exhibit binding to the acceptor molecule; and d) determining the molecular structure of the suitable synthetic receptor(s).
- 46. The method of claim 45, wherein the acceptor molecule introduced is linked to a label.
- 47. The method of claim 46, wherein the label attached to the acceptor molecule introduced identifies the suitable synthetic receptor(s) interacting with the acceptor molecule.
- 48. The method of claim 47, wherein the label is a dye, a fluorescent label or a radioactive label.
- 49. The method of claim 47, wherein the acceptor molecule is an antibody, a peptide, a protein, a carbohydrate, a nucleic acid, a lipid, a drug, a metal or a small molecule.
- 50. The method of claim 49, wherein the protein acceptor molecule is a growth hormone selected from the group comprising human, bovine, porcine, avian, ovine, piscine, and equine growth hormone, and polypeptide analogs thereof having the biological activity of the corresponding naturally occurring growth hormone.
- 51. The method claim 45, wherein the acceptor molecule is present on whole cells, viruses or bacteria.
- 52. The method of claim 45, wherein the acceptor molecule is a cancer cell associated with the following cancers, melanoma, lip, tongue, mouth, pharynx, esophagus, stomach, small intestine, colon, rectal, liver, pancreas, larynx, lung, bone, connective tissue, skin, breast, uterus, ovary, prostate, testis, bladder, kidney, eye, brain, central nervous system, endocrine glands, blood and lymph tissues or leukemia.
- 53. The method of claim 45, wherein the synthetic receptor selectively binds an acceptor molecule in the presence of other different acceptor molecules.
- 54. A method for assaying a synthetic receptor library for suitable synthetic receptor(s) that exhibit biological activity, the method comprising the steps is of:
a) generating the synthetic receptor library of claim 25;b) detecting the biological activity of suitable synthetic receptors of the synthetic receptor library in situ; c) isolating the suitable synthetic receptor(s) that exhibit the biological activity; and d) determining the molecular structure of the suitable synthetic receptor(s) isolated in step (c).
- 55. The method according to claim 54, wherein the biological activity is cytotoxicity, antitumor activity, antibacterial activity, antiviral activity, antifungal activity, anti-parasite activity, growth factor activity, growth inhibitory activity, hormone activity, neurotransmitter activity, immumomodulator activity, regulatory activity or enzymatic activity.
- 56. The method of claim 45 or 54, wherein the activity of interest is determined at nanomolar concentrations.
- 57. The method of claim 45 or 54, to determine a suitable synthetic receptor(s) for use as a therapeutic agent.
- 58. The method of claim 45 or 54, to determine a suitable synthetic receptor(s) for use as a diagnostic agent.
- 59. The method of claim 45, to determine a suitable synthetic receptor(s) for use as a chromatographic separation agent.
- 60. The method of claim 45, wherein the suitable synthetic receptor selectively binds to a transition state analogue.
- 61. A method for assaying a synthetic receptor library for a suitable synthetic receptor(s) which catalyzes a reaction, the method comprising the steps of:
a) generating the synthetic receptor library of claim 25;b) introducing to the synthetic receptor library a substrate such that a catalyzed reaction product is determined; c) isolating the suitable synthetic receptor(s) that exhibits catalytic activity; and d) determining the molecular structure the suitable synthetic receptor(s) isolated in step (c).
- 62. A method for assaying a synthetic receptor library for suitable a synthetic receptor(s) which inhibits an enzyme-catalyzed reaction, the method comprising the steps of:
a) generating the synthetic receptor library of claim 25;b) introducing to the synthetic receptor library an enzyme that catalyzes a reaction of interest in situ; c) detecting inhibition by a suitable synthetic receptor(s) of the enzyme-catalyzed reaction of interest in situ; d) isolating the suitable synthetic receptor(s) that exhibits inhibition of enzyme catalyzed reaction of interest in situ; and e) determining the molecular structure the suitable synthetic receptor(s) isolated in step (c).
- 63. The synthetic receptor of claim 1 having the structure:
- 64. The synthetic receptor of claim 1 having the structure:
- 65. The synthetic receptor of claim 1, wherein the polyfunctional organic template is
Parent Case Info
[0001] This application is a continuation-in-part of U.S. Ser. No. 08/181,628 filed Jan. 13, 1994, the contents of which are incorporated by reference to the subject application.
[0002] Throughout this application, various references are referred to within parentheses. Disclosure of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains.
Government Interests
[0003] The invention was made in part with government funds under Grant CHE92-08254 from the National Science Foundation. Therefore, the U.S. Government has certain rights in the invention.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
PCT/US95/00572 |
1/13/1995 |
WO |
|