Combinatorial complex carbohydrate libraries and methods for the manufacture and uses thereof

• US 20020127599A1
• Filed: 05/21/2001
• Published: 09/12/2002
• Est. Priority Date: 02/17/1999
• Status: Active Grant

• Current Assignee: Glycominds Diagnostics Ltd.
• Original Assignee: Glycominds, Ltd. (Storage Drop Storage Technologies Ltd.)
• Inventors: Dotan, Nir, Dukler, Avinoam
• Granted Patent: US 6,972,172 B2
• Time in Patent Office: Days
• US Class Current: 435/7.1
• CPC Class Codes: B01J 2219/00731 Saccharides
• CPC Class Codes: C07B 2200/11 Compounds covalently bound to a solid support
• CPC Class Codes: C07H 15/02 Acyclic radicals, not substituted by cyclic structures
• CPC Class Codes: C07H 15/203 Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07K 14/59 Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
• CPC Class Codes: C08B 37/00 Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof cellulose D21; microbiological processes C12P
• 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 40/12 Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: G01N 33/5308 for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose
• CPC Class Codes: G01N 33/6842 Proteomic analysis of subsets of protein mixtures with reduced complexity, e.g. membrane proteins, phosphoproteins, organelle proteins
• CPC Class Codes: G01N 33/6845 Methods of identifying protein-protein interactions in protein mixtures

Abstract

A combinatorial complex carbohydrate library is provided and including a plurality of addressable complex carbohydrate structures.

Claims

1. A combinatorial complex carbohydrate library comprising a plurality of addressable complex carbohydrate structures.

2. The combinatorial complex carbohydrate library of claim 1, wherein each of said addressable complex carbohydrate structures is attached to a solid support.

3. The combinatorial complex carbohydrate library of claim 2, wherein attaching each of said addressable complex carbohydrate structures to said solid support is effected by a linker.

4. The combinatorial complex carbohydrate library of claim 3, wherein the linker is cleavable.

5. The combinatorial complex carbohydrate library of claim 4, wherein the linker is cleavable under conditions that are harmless to carbohydrates.

6. The combinatorial complex carbohydrate library of claim 4, wherein the linker is selected so as to allow attaching thereto a p-Nitrophenyl, amine or squaric acid derivative of a sugar.

7. The combinatorial complex carbohydrate library of claim 3, wherein said linker includes at least two contiguous covalent bonds.

8. The combinatorial complex carbohydrate library of claim 3, wherein said linker is selected from the group consisting of an amino acid, a peptide, a non-glycosylated protein, a lipid, a ceramide, dolicol phosphate, a cyclodextrin, an oligosaccharide, a monosaccharide, an alkyl chain and a nucleic acid.

9. The combinatorial complex carbohydrate library of claim 3, wherein said linker is of a length of at least 20 Angstrom.

10. The combinatorial complex carbohydrate library of claim 2, wherein said solid support is selected from the group consisting of addressable microparticles, addressable beads, addressable multi-block and a flat platform.

11. The combinatorial complex carbohydrate library of claim 10, wherein said flat platform is selected from the group consisting of a microtiterplate, a membrane and a chip.

12. The combinatorial complex carbohydrate library of claim 11m wherein said microtiterplate is an addressable microfabricated array of closed reaction chambers supplemented with micro-fluid systems.

13. The combinatorial complex carbohydrate library of claim 12, wherein said closed reaction chambers are arranged at a density of 4-25 per square cm.

14. The combinatorial complex carbohydrate library of claim 12, wherein each of said closed reaction chambers is of 50-1000 nanoliter in volume.

15. The combinatorial complex carbohydrate library of claim 2, wherein said solid support is a chip and further wherein different complex carbohydrate structures of said plurality of addressable complex carbohydrate structures are arrange in patches spaced not more than 2.25 mm from one another center to center.

16. The combinatorial complex carbohydrate library of claim 2, wherein said solid support is of a substance selected from the group consisting of polysterene cross-linked with divinylbenzene, polyethylene glycol-polystyrene block copolymer, polyamides, polyacrylamide, polymethacrylamide, silica, glass, quartz, plastic and cellulose.

17. The combinatorial complex carbohydrate library of claim 1, wherein at least one of said plurality of addressable complex carbohydrate structures includes at least two contiguous saccharide units of a single species.

18. The combinatorial complex carbohydrate library of claim 1, wherein at least one of said plurality of addressable complex carbohydrate structures includes at least one branch.

19. The combinatorial complex carbohydrate library of claim 18, wherein at least one of said at least one branch is formed of identical core and branching saccharide units.

20. The combinatorial complex carbohydrate library of claim 1, wherein at least one of said plurality of addressable complex carbohydrate structures includes at least 4 saccharide units.

21. The combinatorial complex carbohydrate library of claim 1, wherein at least one of said plurality of addressable complex carbohydrate structures includes at least 5 saccharide units.

22. The combinatorial complex carbohydrate library of claim 1, wherein at least one of said plurality of addressable complex carbohydrate structures includes at least 6 saccharide units.

23. The combinatorial complex carbohydrate library of claim 1, wherein at least one of said plurality of addressable complex carbohydrate structures includes at least 7 saccharide units.

24. The combinatorial complex carbohydrate library of claim 1, wherein said plurality of addressable complex carbohydrate structures are a representation including non-natural complex carbohydrates.

25. The combinatorial complex carbohydrate library of claim 1, wherein said plurality of addressable complex carbohydrate structures are a representation including natural complex carbohydrates.

26. The combinatorial complex carbohydrate library of claim 25, wherein said natural complex carbohydrates are derived from a human source.

27. The combinatorial complex carbohydrate library of claim 26, wherein said human source is selected from the group consisting of a tissue, cells and body fluids.

28. The combinatorial complex carbohydrate library of claim 1, wherein said plurality of addressable complex carbohydrate structures are a representation of domains of at least one natural complex carbohydrate.

29. The combinatorial complex carbohydrate library of claim 28, wherein said at least one natural complex carbohydrate is derived from a human resource.