Screening of drugs from chemical combinatorial libraries employing transponders

• US 6,387,623 B1
• Filed: 03/29/2000
• Issued: 05/14/2002
• Est. Priority Date: 11/30/1995
• Status: Expired due to Fees

• Current Assignee: PharmaSeq, Inc.
• Original Assignee: PharmaSeq, Inc.
• Inventors: Mandecki, Wlodek
• Primary Examiner(s): Campbell, Eggerton A.
• Application Number:
  US09/537,620
• Time in Patent Office: 776 Days
• Field of Search: 435/6, 435/91.2, 435/7.1
• US Class Current: 435/6.11
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00567 Transponder chips
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00592 Split-and-pool, mix-and-divide processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: C07K 1/042 characterised by the nature of the carrier
• CPC Class Codes: C07K 1/047 Simultaneous synthesis of different peptide species; Peptide libraries
• CPC Class Codes: C40B 40/10 Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 70/00 Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: G01N 15/14 Optical investigation techniques, e.g. flow cytometry

Abstract

Materials and methods are disclosed for identifying chemical compounds having desired binding properties towards a binding partner of pharmaceutical interest. The method employs transponders associated with the solid phase material used in the assay and a scanner to encode and decode data stored electronically on the transponder. The data stored on the transponder identifies the monomeric building blocks added during the synthesis. The structural identification of synthesized compounds bound to the solid phase is done by decoding the transponder.

Claims

1. A method of screening a compound for binding to a target biomolecule of pharmaceutical interest, comprising the steps of:

(a) providing a solid phase having a transponder associated with the solid phase and the compound attached to a surface of the solid phase, wherein the transponder comprises of memory elements containing data indicating the identity of the compound, a radio-frequency transmitter and one or more photovoltaic cells providing a source of electrical power for the transponder when illuminated by light;

(b) providing a fluorescently labeled form of the target biomolecule;

(c) incubating the solid phase having the compound attached thereto with the fluorescently labeled biomolecule;

(d) analyzing the solid phase using the light to detect any fluorescently labeled target biomolecule directly or indirectly attached to the compound; and

(e) decoding the transponder memory elements to determine the identity of the compound.

2. The method of claim 1, wherein the compound is a peptide.

3. The method of claim 1, wherein the compound is a small organic molecule.

4. The method of claim 1, wherein the solid phase comprises a surface of the transponder.

5. The method of claim 1, wherein one or more layers of coating are deposited on an outer surface of the transponder and the compound is attached to a coating layer.

6. The method of claim 5, wherein the layers of coating comprise of glass, latex or plastic.

7. The method of claim 1, wherein the solid phase is particulate.

8. A method of screening a compound for binding to a target biomolecule of pharmaceutical interest, comprising the steps of:

(a) providing a solid phase having a transponder associated with the solid phase and having a chemical scaffold attached to a surface of the solid phase, the scaffold having active groups, and the transponder comprising of memory elements, a radio-frequency transmitter and one or more photovoltaic cells providing a source of electrical power for the transponder when illuminated by light;

(b) sequentially adding chemical substituents to the active groups on the scaffold to synthesize the compound;

(c) encoding data on the transponder memory elements to indicate each substituent added;

(d) providing a fluorescently labeled form of the target biomolecule;

(e) incubating the solid phase having the compound attached thereto with the fluorescently labeled biomolecule;

(f) analyzing the solid phase using the light to detect any fluorescently labeled target biomolecule directly or indirectly attached to the compound; and

(g) decoding the transponder memory elements to determine the identity of the synthesized compound.

9. The method of claim 8, wherein the solid phase comprises a surface of the transponder.

10. The method of claim 8, wherein one or more layers of coating are deposited on an outer surface of the transponder and the compound is attached to a coating layer.

11. The method of claim 10, wherein the layers of coating comprise of glass, latex or plastic.

12. The method of claim 8, wherein the solid phase is particulate.

13. A method of screening a compound for binding to a target biomolecule of pharmaceutical interest, comprising the steps of:

(a) providing a solid phase having a transponder associated with the solid phase and having a chemical scaffold attached to a surface of the solid phase, the scaffold having active groups, and the transponder comprising of memory elements containing an unique identifier, a radio-frequency transmitter and one or more photovoltaic cells providing a source of electrical power for the transponder when illuminated by light;

(b) sequentially adding chemical substituents to the active groups on the scaffold to synthesize the compound;

(c) associating the unique identifier with the identity of the chemical substituents;

(d) providing a fluorescently labeled form of the target biomolecule;

(e) incubating the solid phase having the compound attached thereto with the fluorescently labeled biomolecule;

(f) analyzing the solid phase using the light to detect any fluorescently labeled target biomolecule directly or indirectly attached to the compound; and

(g) decoding the transponder memory elements to determine the identity of the synthesized compound.

14. The method of claim 13, wherein the solid phase comprises a surface of the transponder.

15. The method of claim 13, wherein one or more layers of coating are deposited on an outer surface of the transponder and the compound is attached to a coating layer.

16. The method of claim 15, wherein the layers of coating comprise of glass, latex or plastic.

17. The method of claim 13, wherein the solid phase is particulate.

18. A method of screening compounds for binding to a target biomolecule of pharmaceutical interest, comprising the steps of:

(a) providing a particulate solid phase having a transponder associated with each particle and a chemical scaffold having active groups attached to a surface of the particle, wherein the transponder comprises of memory elements, a radio-frequency transmitter and one or more photovoltaic cells providing a source of electrical power for the transponder when illuminated by light;

(b) dividing the particles randomly into groups;

(c) sequentially adding chemical substituents to the active groups on the scaffold to synthesize the compounds, encoding data on the transponder for each addition to indicate the substituent added, combining the groups and redividing the particles into groups after each addition;

(d) repeating the addition, combining and re-dividing steps until all active groups on the scaffold have been reacted;

(e) providing a fluorescently labeled form of the target biomolecule;

(f) incubating the particles having the synthesized compounds attached thereto with the fluorescently labeled target biomolecule;

(g) analyzing the particles using the light to detect any fluorescently labeled target biomolecule directly or indirectly attached to the compounds; and

(h) decoding the transponder memory elements to determine the identity of the synthesized compounds on the particles analyzed.

19. The method of claim 18, wherein the solid phase comprises a surface of the transponder.

20. The method of claim 18, wherein one or more layers of coating are deposited on an outer surface of the transponder and the compound is attached to a coating layer.

21. The method of claim 20, wherein the layers of coating comprise of glass, latex or plastic.

22. A method of screening compounds for binding to a target biomolecule of pharmaceutical interest, comprising the steps of:

(a) providing a particulate solid phase having a transponder associated with each particle and a chemical scaffold having active groups attached to a surface of the particle, wherein the transponder comprises of memory elements containing an unique identifier, a radio-frequency transmitter and one or more photovoltaic cells providing a source of electrical power for the transponder when illuminated by light;

(b) dividing the particles randomly into groups;

(c) sequentially adding chemical substituents to the active groups on the scaffold to synthesize the compounds, combining the groups and re-dividing the particles into groups after each addition;

(d) repeating the addition, combining and re-dividing steps until all active groups on the scaffold have been reacted;

(e) associating the unique identifiers with the identity of the chemical substituents;

(f) providing a fluorescently labeled form of the target biomolecule;

(g) incubating the particles having the synthesized compounds attached thereto with the fluorescently labeled target biomolecule;

(h) analyzing the particles using the light to detect any fluorescently labeled target biomolecule directly or indirectly attached to the compounds; and

(i) decoding the unique identifiers in the transponder memory elements to determine the identity of the synthesized compounds on the particle analyzed.

23. The method of claim 22, wherein the solid phase comprises a surface of the transponder.

24. The method of claim 22, wherein one or more layers of coating are deposited on an outer surface of the transponder and the compound is attached to a coating layer.

25. The method of claim 24, wherein the layers of coating comprise of glass, latex or plastics.