Small molecule printing

• US 6,824,987 B1
• Filed: 05/10/2000
• Issued: 11/30/2004
• Est. Priority Date: 05/11/1999
• Status: Expired due to Fees

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation), Howard Hughes Medical Institute
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Depew, Kristopher M., Koehler, Angela N., Hergenrother, Paul, MacBeath, Gavin, Schreiber, Stuart L.
• Primary Examiner(s): CELSA, BENNETT M
• Application Number:
  US09/567,910
• Time in Patent Office: 1,665 Days
• Field of Search: 435/7.1, 435/287.1, 435/287.2, 435/288.4, 436/501, 436/518, 436/809
• US Class Current: 506/32
• 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 2219/00387 Applications using probes
• CPC Class Codes: B01J 2219/00454 by chemical cleavage from the solid support
• CPC Class Codes: B01J 2219/00459 Beads
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00533 essentially rectangular
• 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 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/0072 Organic compounds
• CPC Class Codes: C07B 2200/11 Compounds covalently bound to a solid support
• CPC Class Codes: C07C 311/49 to nitrogen atoms
• CPC Class Codes: C40B 30/04 by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
• CPC Class Codes: C40B 40/04 Libraries containing only organic compounds
• CPC Class Codes: C40B 50/14 Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 31/00 Investigating or analysing non-biological materials by the use of the chemical methods specified in the subgroup; Apparatus specially adapted for such methods
• CPC Class Codes: G01N 33/54353 with ligand attached to the carrier via a chemical coupling agent coatings G01N33/54393
• CPC Class Codes: Y10S 436/809 : Multifield plates or multicontainer arrays

Abstract

The present invention provides compositions and methods to facilitate the identification of compounds that are capable of interacting with a biological macromolecule of interest. In one aspect, a composition is provided that comprises an array of one or more types of chemical compounds attached to a solid support, wherein the density of the array of compounds is at least 1000 spots per cm². In particularly preferred embodiments, these compounds are attached to the solid support through a covalent interaction. In general, these inventive arrays are generated by: (1) providing a solid support, wherein said solid support is functionalized with a selected chemical moiety capable of interacting with a desired chemical compound to form an attachment; (2) providing one or more solutions of one or more types of compounds to be attached to the solid support; and (3) delivering said one or more types of compounds to the solid support, whereby an array is formed and the array of compounds has a density of at least 1000 spots per cm². In another aspect, the present invention provides methods for utilizing these arrays to identify small molecule partners for biological macromolecules of interest comprising: (1) providing an array of compounds, wherein the array has a density of at least 1000 spots per cm²; (2) contacting the array with one of more types of biological macromolecules of interest; and (3) determining the interaction of specific small molecule-biological macromolecule partners.

Claims

1. An array comprising a plurality of more than one type of non-oligomeric compounds attached to a solid support,

wherein the density of said array of compounds is at least 1000 spots per cm²;

and

wherein the compounds are attached to the solid support as depicted;

 

wherein

X is O, S, or NH;

m is an integer between 0 and 5;

n is an integer between 0 and 5; and

R is the compound attached to the solid support.

2. The array of claim 1, wherein said array of chemical compounds comprises an array of non-peptidic and non-oligomeric chemical compounds.

3. The array of claim 1, wherein each of said chemical compounds in said array is attached to the solid support through a covalent interaction.

4. The array of claim 1, wherein said covalent interaction is characterized in that the linkage is robust enough so that the compounds are (1) not inadvertently cleaved during subsequent manipulation steps and (2) inert so that the functionalities employed do not interfere with subsequent manipulation steps.

5. The array of claim 1, wherein each of said chemical compounds in said array is attached to the solid support through a linkage generated by a Michael addition.

6. The composition of claim 1, wherein the solid support is glass.

7. The array of claim 1, wherein said array of chemical compounds comprises an array of small molecules.

8. The array of claim 1, wherein the density of said array of compounds is at least 5000 spots per cm².

9. The array of claim 1, wherein the density of said array of compounds is at least 10,000 spots per cm².