Synthetic receptors

• US 6,797,522 B1
• Filed: 03/12/1998
• Issued: 09/28/2004
• Est. Priority Date: 01/13/1994
• Status: Expired due to Fees

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Wennemers, Helma, Li, Ge, Still, W. Clark
• Primary Examiner(s): Ponnaluri, Padmashri
• Application Number:
  US09/041,343
• Time in Patent Office: 2,392 Days
• Field of Search: 435/6, 435/7.1, 436/501, 436/518, 436/528, 436/529, 436/531, 436/534, 530/333, 530/334, 536/1.11, 536/23.1, 536/25.3, 544/1, 544/2, 548/100
• US Class Current: 436/518
• CPC Class Codes: B01J 2219/0054 Means for coding or tagging the apparatus or the reagents
• CPC Class Codes: B01J 2219/00572 Chemical means
• CPC Class Codes: B01J 2219/00592 Split-and-pool, mix-and-divide processes
• CPC Class Codes: C07J 41/0055 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
• CPC Class Codes: C07J 41/0061 one of the carbon atoms being part of an amide group
• CPC Class Codes: C07J 9/005 containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
• CPC Class Codes: C07K 1/047 Simultaneous synthesis of different peptide species; Peptide libraries
• CPC Class Codes: C07K 5/123 Tripeptides
• CPC Class Codes: C40B 70/00 Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes

Abstract

The invention is directed to synthetic receptor(s) 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. The template may be linked to an identifier which uniquely defines the synthetic receptor. The identifier is a stable chemical molecule or a plurality of stable chemical molecules distinguishable and detectable to picomolar levels or may be an oligonucleotide. In a preferred embodiment, the template is covalently linked to a solid support which is linked to an identifier. In addition, the invention includes methods of preparing synthetic receptors and synthetic receptor libraries. The synthetic library may be linked with identifiers such that the library comprises a plurality of different synthetic receptor members. The invention also provides methods for assaying a synthetic receptor library to determine suitable synthetic receptor(s) which (a) bind an acceptor molecule; (b) exhibit biological activity; (c) which catalyze a reaction or inhibit a catalyzed reaction; and (d) separate compounds in chromatography.

Claims

1. A synthetic receptor comprising a polyfunctional organic template covalently linked to two or more oligomers;

said template being a monocyclic nitrogen heterocycle substituted with two or more —

O—

, —

NH—

or —

C═

O to which oligomers are attached;

said oligomers chosen independently from the group consisting of straight chained, cyclic and branched oligoamide, oligourea, oligourethane, oligosulfonamide and peftide oligomers;

said oligomers comprising three or more monomers; and

said —

O—

, —

NH—

or —

C═

O to which an oligomer is attached forming an amide, urea, urethane, sulfonamide or ester bond with said oligomer.

2. A synthetic receptor according to claim 1 wherein said template is chosen from diaminoazepine, diaminopiperidine and diaminopyrrolidine.

3. A synthetic receptor according to claim 2 wherein said template is a diaminoazepine.

4. A synthetic receptor according to claim 3 wherein said oligomers are cyclic oligoamides and a diamine component of said oligoamide is a diaminoazepine.

5. A synthetic receptor according to claim 2 wherein said template is a diaminopyrrolidine.

6. A synthetic receptor comprising a polyfunctional organic template covalently linked to two or more oligomers and to a solid support;

said template being a monocyclic nitrogen heterocycle substituted with two or more —

O—

, —

NH—

or —

C═

O to which oligomers are attached;

said oligomers chosen independently from the group consisting of straight chained, cyclic and branched oligoamide, oligourea, oligourethane, oligosulfonamide and peptide oligomers;

said oligomers comprising three or more monomers; and

said —

O—

, —

NH—

or —

C═

O to which an oligomer is attached forming an amide, urea, urethane, sulfonamide or ester bond with said oligomer.

7. A synthetic receptor according to claim 6 wherein said template is chosen from diaminoazepine, diaminopiperidine and diaminopyrrolidine.

8. A synthetic receptor according to claim 7 wherein said template is a diaminoazepine.

9. A synthetic receptor according to claim 8 wherein said oligomers are cyclic oligoamides and a diamine component of said oligoamide is a diaminoazepine.

10. A synthetic receptor according to claim 7 wherein said template is a diaminopyrrolidine.

11. A synthetic receptor according to claim 10 wherein said polyfunctional organic template covalently linked to a solid support is

n is 2 or 3;

and Q is a solid support or a solid support linked to an identifier.

12. A synthetic receptor according to claim 10 wherein said synthetic receptor has the structure

wherein

n is 2 or 3;

and Q is a solid support or a solid support linked to an identifier.

13. A synthetic receptor according to claim 10 wherein said synthetic receptor has the structure

wherein

n is 2 or 3;

and Q is a solid support or a solid support linked to an identifier.

14. A synthetic receptor according to claim 6, wherein the solid support is a particle composed of cellulose, controlled-pore glass, silica gel, polystyrene, PEG-polystyrene, polystyrene optionally cross-linked with divinylbenzene, polyacrylamide, 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.