Chemically encoded spatially addressed library screening platforms

Patent metadata

Field	Value
Publication number	US-11015266-B2
Application number	US-202016943630-A
Country	US
Kind code	B2
Filing date	Jul 30, 2020
Priority date	Feb 24, 2015
Publication date	May 25, 2021
Grant date	May 25, 2021

Abstract

Provided herein are encoded split pool libraries useful, inter alia, for forming highly diverse and dense arrays for screening and detection of a variety of molecules.

First claim

What is claimed is:

1. A microparticle immobilized on solid support, wherein said microparticle is covalently attached to:
(i) a ligand domain through a first linker; and
(ii) a nucleic acid domain through a second linker,
wherein said nucleic acid domain identifies said ligand domain;
wherein said ligand domain is selected from the group consisting of a peptide, a small molecule, and a protein;
wherein said second linker comprises an acyl group, a sulfonamide group, or a photocleavable group; and
wherein said nucleic acid domain is removable under a condition that said ligand domain is not removable.

2. The microparticle of claim 1 , wherein said ligand domain comprises a removable protecting moiety covalently attached to a reactive moiety.

3. The microparticle of claim 2 , wherein said reactive moiety is selected from the group consisting of a carboxylic acid, an amine, a thiol, or an alcohol.

4. The microparticle of claim 2 , wherein said removable protecting moiety comprises an amino acid side chain, an amino terminus, or a carboxy terminus.

5. The microparticle of claim 1 , wherein said microparticle is selected from the group consisting of a functionalized microbead, a magnetic microbead, a metallic microbead, a polymeric microbead, a silica microbead, a dendrimer, and a branched polymer.

6. The microparticle of claim 1 , wherein said peptide is selected from the group consisting of a macrocyclic peptide, an acyclic precursor to a macrocyclic peptide, a peptidomimetic, a polyamide, and a macrolactam.

7. The microparticle of claim 1 , wherein said peptide further comprises non-peptide functionality.

8. The microparticle of claim 1 , wherein said ligand domain is bound to a ligand binder.

9. The microparticle of claim 1 , wherein said ligand domain comprises a plurality of ligand domains attached through a plurality of first linkers.

10. The microparticle of claim 1 , wherein said nucleic acid domain comprises a plurality of nucleic acid domains attached through a plurality of second linkers.

11. The microparticle of claim 1 , wherein said nucleic acid sequence is bound to a detectably labeled complementary nucleic acid sequence.

12. A high density ordered array, said high density ordered array comprising a solid support comprising a plurality of wells, wherein each of said plurality of wells further comprises an immobilized microparticle, and wherein each of said immobilized microparticle is covalently attached to:
(i) a ligand domain through a first linker; and
(ii) a nucleic acid domain through a second linker;
wherein said nucleic acid domain identifies said ligand domain;
wherein said ligand domain is selected from the group consisting of a peptide, a small molecule, and a protein;
wherein said second linker comprises an acyl group, a sulfonamide group, or a photocleavable group; and
wherein said nucleic acid domain is removable under a condition that said ligand domain is not removable.

13. The high density ordered array of claim 12 , wherein said ligand domain comprises a removable protecting moiety attached to a reactive moiety.

14. The high density ordered array of claim 12 , wherein said ligand domain is bound to a ligand binder.

15. The high density ordered array of claim 12 , wherein said peptide is selected from the group consisting of a macrocyclic peptide, an acyclic precursor to a macrocyclic peptide, a peptidomimetic, a polyamide, and a macrolactam.

16. The high density ordered array of claim 12 , wherein said peptide further comprises non-peptide functionality.

17. The high density ordered array of claim 12 , wherein said high density ordered array includes at least 10,000 microparticles per square millimeter.

18. The s high density ordered array of claim 17 , wherein said high density ordered array includes at least 50,000 microparticles per square millimeter.

19. The high density ordered array of claim 18 , wherein said high density ordered array includes at least 150,000 microparticles per square millimeter.

20. The high density ordered array of claim 19 , wherein said high density ordered array includes at least 250,000 microparticles per square millimeter.

21. The high density ordered array of claim 12 , wherein said high density ordered array comprises between 10 6 to 10 11 of said immobilized microparticles.

22. The high density ordered array of claim 12 , wherein said condition is selected from the group consisting of UV irradiation, light irradiation, trifluoroacetic acid, ammonium hydroxide, ammonia, methylamine, and a mixture of ammonium hydroxide and methylamine.

23. The high density ordered array of claim 12 , wherein said ordered array is a square packed array or a hexagonal array.

24. The high density ordered array of claim 12 , wherein said second linker is a photocleavable linker, an acid labile linker, or an alkali labile linker.

25. The high density ordered array of claim 12 , wherein said nucleic acid domain is bound to a detectably labeled complementary nucleic acid sequence.

26. The high density ordered array of claim 12 , wherein said high density ordered array is within a detection device, wherein said detection device detects said ligand binder bound to said ligand domain and identifies a location of said bound ligand binder on said solid support.

Assignees

• Hope City

Inventors

• Berlin Jacob
• COPELAND Gregory
• Elison Kathleen
• Muradyan Hurik

Classifications

• C40B70/00 Primary

  Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes · CPC title

• C40B50/16 Primary

  involving encoding steps · CPC title

• G01N33/54313

  the carrier being characterised by its particulate form · CPC title

• G01N33/54326

  Magnetic particles · CPC title

• G01N33/54346

  Nanoparticles · CPC title