Protein chips for high throughput screening of protein activity

• US 8,399,383 B2
• Filed: 05/04/2001
• Issued: 03/19/2013
• Est. Priority Date: 05/04/2000
• Status: Expired due to Fees

• Current Assignee: Yale University
• Original Assignee: Yale University
• Inventors: Snyder, Michael, Reed, Mark, Zhu, Heng, Klemic, James Frank
• Primary Examiner(s): WESSENDORF, TERESA D
• Application Number:
  US09/849,781
• Publication Number:
  US 20030207467A1
• Time in Patent Office: 4,337 Days
• Field of Search: 435/6, 435/7.1, 435/7.5, 435/287.1, 435/288.3, 435/288.4, 435/287.9, 436/518, 436/524, 436/525, 436/527, 436/528, 436/86, 422/50, 422/55, 422/67, 422/82.05, 422/65, 506/14, 506/13
• US Class Current: 506/14
• 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 2219/00274 Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
• CPC Class Codes: B01J 2219/00313 the reactor vessels being formed by arrays of wells in blocks
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00382 Stamping
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01L 3/5085 : for multiple samples, e.g. microtitration plates
• CPC Class Codes: B82Y 15/00 : Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/485 : involving kinase
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2500/00 : Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 33/5008 : for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
• CPC Class Codes: G01N 33/5041 : involving analysis of members of signalling pathways
• CPC Class Codes: G01N 33/543 : with an insoluble carrier for immobilising immunochemicals
• CPC Class Codes: G01N 33/54313 : the carrier being characterised by its particulate form

Abstract

The present invention relates to protein chips useful for the large-scale study of protein function where the chip contains densely packed reaction wells. The invention also relates to methods of using protein chips to assay simultaneously the presence, amount, and/or function of proteins present in a protein sample or on one protein chip, or to assay the presence, relative specificity, and binding affinity of each probe in a mixture of probes for each of the proteins on the chip. The invention also relates to methods of using the protein chips for high density and small volume chemical reactions. Also, the invention relates to polymers useful as protein chip substrates and methods of making protein chips. The invention further relates to compounds useful for the derivatization of protein chip substrates.

Claims

1. A positionally addressable array comprising a plurality of different substances on a solid support, with each different substance being at a different position on the solid support, wherein the density of the different substances on the solid support is at least 100 different substances per cm², and wherein the plurality of different substances comprises at least 61 purified active kinases or functional kinase domains thereof of a mammal, that phosphorylates Serine/Threonine or tyrosine 61 purified active kinases or functional kinase domains thereof of a yeast, that phosphorylates Serine/Threonine or tyrosine or 61 purified active kinases or functional kinase domains thereof of a Drosophila that phosphorylates Serine/Threonine or tyrosine.

2. The array of claim 1 wherein the density of the different substances on the array is between 100 and 1,000 different substances per cm².

3. The array of claim 1 wherein the density of the different substances on the array is between 1,000 and 10,000 different substances per cm².

4. The array of claim 1 wherein the density of the different substances on the array is between 10,000 and 100,000 different substances per cm².

5. The array of claim 1 wherein the density of the different substances on the array is between 100,000 and 1,000,000 different substances per cm².

6. The array of claim 1 wherein the density of the different substances on the array is between 1,000,000 and 10,000,000 different substances per cm².

7. The array of claim 1 wherein the density of the different substances on the array is between 10,000,000 and 25,000,000 different substances per cm².

8. The array of claim 1 wherein the density of the different substances on the array is at least 25,000,000 different substances per cm².

9. The array of claim 1 wherein the density of the different substances on the array is at least 10,000,000,000 different substances per cm².

10. The array of claim 1 wherein the density of the different substances on the array is at least 10,000,000,000,000 different substances per cm².

11. The array of claim 1 wherein the solid support is a glass slide.

12. The array of claim 1 wherein the plurality of different substances are attached to the solid support via a 3-glycidoxypropyl-trimethoxysilane linker.

13. The array of claim 1 wherein the mammal is selected from the group consisting of human, primate, mouse, rat, cat, dog, horse, and cow.

14. The array of claim 13, wherein the organism is human.

15. The array of claim 13, wherein the organism is mouse.

16. The array of claim 13, wherein the organism is mouse.

17. The array of claim 13, wherein the organism is rat.

18. The positionally addressable protein array of claim 1, wherein the plurality of different substances comprises 61 different purified active kinases of an organism.

19. The positionally addressable protein array of claim 1, wherein the plurality of different substances comprises 92 different purified active kinases of a mammal, a yeast, or a Drosophila.

20. The positionally addressable protein array of claim 1, wherein the plurality of different substances comprises 110 different purified active kinases of a mammal, a yeast, or a Drosophila.

21. The positionally addressable protein array of claim 1, wherein the plurality of different substances comprises 116 different purified active kinases of a mammal, a yeast, or a Drosophila.

22. The positionally addressable protein array of claim 1, wherein the plurality of different substances comprises 119 different purified active kinases of a mammal, a yeast, or a Drosophila.

23. The positionally addressable protein array of claim 1, wherein the plurality of different substances comprises 122 purified active different kinases of a mammal, a yeast, or a Drosophila.

24. The positionally addressable array of claim 1, wherein the kinases are yeast kinases.

25. The positionally addressable array of claim 1, wherein the different substances are 61 purified active kinases.

26. The positionally addressable array of claim 25, wherein the kinases are serine/threonine kinase family members, tyrosine kinase family members, or serine/threonine kinase and tyrosine kinase family members.

27. The positionally addressable array of claim 1, wherein the functional kinase domains are functional kinase domains of serine/threonine kinase family members, functional kinase domains of tyrosine kinase family members, functional kinase domains of serine/threonine kinase family members or functional kinase domains of tyrosine kinase family members.

28. The positionally addressable array of claim 25, wherein the 61 purified active kinases are at least 100 amino acids in length.