US2008085838A1PendingUtilityA1
Combinatorial complex carbohydrate libraries and methods for the manufacture and uses thereof
Est. expiryFeb 17, 2019(expired)· nominal 20-yr term from priority
C07H 15/02G01N 2333/42G01N 33/6842G01N 2400/02C40B 30/04C07B 2200/11G01N 33/543G01N 33/6845C07K 14/59G01N 33/66G01N 2400/10C07H 15/203G01N 33/5308
60
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Claims
Abstract
A combinatorial complex carbohydrate library is provided and including a plurality of addressable complex carbohydrate structures.
Claims
exact text as granted — not AI-modified1 . A method diagnosing a disease, a disorder or a condition characterized by elicitation of antibodies against a carbohydrate structure, the method comprising:
(a) providing an addressable carbohydrate library, wherein said addressable carbohydrate library comprises a plurality of carbohydrate structures each being attached at a specific and addressable location of a single solid support, wherein each of said plurality of carbohydrate structures is composed of monosaccharide residues, such that a stereo-specificity of each bond interconnecting said monosaccharide residues is defined by said addressable location on said single solid support; (b) reacting the addressable carbohydrate library with antibodies derived from a patient suspected of having the disease, disorder or condition to thereby generate a pattern of locations to which the antibodies bind, such that by comparing the pattern with a known pattern a diagnosis of the disease, disorder or condition is obtainable.
2 . The method of claim 1 , wherein each of said plurality of carbohydrate structures is attached to said single solid support via a linker.
3 . The method of claim 2 , 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.
4 . The method of claim 2 , wherein said linker comprises at least one cyanuric chloride derivatives and an aniline group.
5 . The method of claim 1 , wherein said single solid support is a flat platform.
6 . The method of claim 5 , wherein said single solid support is a chip and further wherein different carbohydrate structures of said plurality of carbohydrate structures are arranged on said chip in patches spaced not more than 2.25 mm from one another, center to center.
7 . The method of claim 1 , wherein said single solid support is of a substance selected from the group consisting of polystyrene cross-linked with divinylbenzene, polyethylene glycol-polystyrene block copolymer, polyamides, polyacrylamide, polymethacrylamide, silica, glass, quartz, plastic and cellulose.
8 . The method of claim 1 , wherein at least one of said plurality of carbohydrate structures comprises at least two covalently attached identical saccharide units.
9 . The method of claim 1 , wherein at least one of said plurality of carbohydrate structures comprises at least one branch.
10 . The method of claim 1 , wherein at least one of said plurality of carbohydrate structures comprises at least 4 saccharide units.
11 . The method of claim 1 , wherein at least one of said plurality of carbohydrate structures comprises at least 5 saccharide units.
12 . The method of claim 1 , wherein at least one of said plurality of carbohydrate structures comprises at least 6 saccharide units.
13 . The method of claim 1 , wherein at least one of said plurality of carbohydrate structures comprises at least 7 saccharide units.
14 . The method of claim 1 , wherein at least a portion of said plurality of carbohydrate structures are not naturally occurring carbohydrate structures.
15 . The method of claim 1 , wherein at least a portion of said plurality of carbohydrate structures are structurally identical to naturally occurring carbohydrate structures.
16 . The method of claim 15 , wherein said naturally occurring carbohydrate structures are present in human cells.
17 . The method of claim 15 , wherein said naturally occurring carbohydrate structures are derived from tissue, cells and/or body fluids of a human.
18 . The method of claim 15 , wherein at least a portion of said plurality of carbohydrate structures are structurally identical to domains of at least one naturally occurring carbohydrate structure.
19 . The method of claim 18 , wherein said at least one naturally occurring carbohydrate is present in human cells.
20 . The method of claim 1 , wherein said plurality of carbohydrate structures comprise at least two structures selected from the group consisting of:
Fuc(α1,2)Gal(β) NeuAC(a2,3)Gal(β1,3)GlcNAc(α) NeuAC(a2,3)Gal(β1,3)GlcNAc(β) NeuAC(a2,6)Gal(β1,4)GlcNAc(α) NeuAC(a2,6)Gal(β1,4)GlcNAc(β) NeuAC(a2,3)Gal(β1,4)GlcNAc(α) Fuc(α1,2)[Gal(β1,4)]GlcNAc(β) Fuc(α1,2)[Gal(β1,4)]GlcNAc(β) Fuc(α1,6)[Man(β1,4)GlcNAc(β1,4)]GlcNAc(β) Man(β1,4)GlcNAc(β1,4)GlcNAc(β) Man(α1,2)Man(α1,2) Man(α) Man(α1,3)Man(α1,2)Man(α1,2) Man(α) Gal(α1,3)Gal(β1,4)GlcNAc(β) GalNAc(α1,3)[Fuc(α1,2)]Gal(β) GalNAc(β1,4)[NeuAC(a2,3)]Gal(β1,4)GlcNAc(β) GlcA(β1,3)Gal(β1,3)Gal(β1,4)Xyl(β) GlcNAc(β1,6)Gal(β1,4)GlcNAc(β) GlcNAc(β1,6)GalNAc(β1,3)Gal(α) GlcNAc(β1,2) Man(α1,3)[Man(α1,6)]Man(β) GlcNAc(β1,2) Man(α1,3)[Man(α1,6)]Man(β) NeuAC(α2,6)GalNAc(α) Fuc(α1,2)Gal(β) Fuc(α1,2)[Gal(β1,4)]GlcNAc(β) Fuc(α1,6)GlcNAc(β) Fuc(α1,3)Glc(β) Fuc(α1,4)GlcNAc(β) Fuc(α1,3)GlcNAc(β) Gal(β1,3)GlcNAc(α) Gal(β1,3)GlcNAc(β) Gal(β1,4)Xyl(β) Gal(β1,3)GlcNAc(β) GlcNAc(β1,3)GalNAc(β) GlcNAc(β1,3)GalNAc(α) GlcNAc(β1,4)GlcNAc(α) GlcNAc(β1,4)GlcNAc(β) GlcNAc(β1,6)Gal(α) GlcNAc(β1,6)Gal(β) GlcNAc(β1,3)Gal(α) GlcNAc(β1,3)Gal(β) Gal(β1,3)GlcNAc(β1,3)Gal(β1,4)Glc(β) Gal(β1,4)GlcNAc(β1,3)Gal(β1,4)Glc(β) Gal(β1,3)GlcNAc(β1,3)Gal(β) Gal(β1,4)GlcNAc(β1,6)Gal(β) Gal(β1,4)GlcNAc(β1,3)Gal(β) Fuc(α1,3)GlcNAc(β1,6)Gal(β) Fuc(α1,4)GlcNAc(β1,3)Gal(β) Fuc(α1,2)Gal(β1,3)GlcNAc(β) Fuc(α1,2)Gal(β1,4)GlcNAc(β) Fuc(α1,3)GlcNAc(β1,3)Gal(β) Fuc(α1,3)GlcNAc(β1,3)Gal(β1,4)Glc(β) Fuc(α1,4)GlcNAc(β1,3)Gal(β1,4)Glc(β) Fuc(α1,3)GlcNAc(β1,6)Gal(β1,4)Glc(β) Gal(β1,4)GlcNAc(β1,6)Gal(β1,4)Glc(β) Gal(β1,4)GlcNAc(β1,3)Gal(β1,4)Glc(β) Gal(β1,3)GlcNAc(β1,6)Gal(β1,4)Glc(β) Fuc(α1,2)Gal(β1,3)GlcNAc(β1,3)Gal(β) Fuc(α1,2)Gal(β1,4)GlcNAc(β1,3)Gal(β) GlcNAc(β1,3)Gal(β1,4)GlcNAc(β1,3)Gal(β) Fuc(α1,2)[Gal(β1,4)]Glc(β) Fuc(α1,3)[Gal(β1,4)]GlcNAc(β) GlcNAc(β1,3)[GlcNAc(β1,6)]Gal(β) Fuc(α1,4)[Gal(β1,3)]GlcNAc(β) GlcNAc(β1,3)[GlcNAc(β1,6)]Gal(β) Fuc(α1,3)[Gal(β1,4)]GlcNAc(β1,3)Gal(β) Fuc(α1,3) [Fuc(α1,2)Gal(β1,4)]GlcNAc(β) Fuc(α1,4) [Gal(β1,3)]GlcNAc(1,3)Gal(β) Fuc(α1,2)Gal(β1,4)[Fuc(α1,3)]GlcNAc(β) Fuc(α1,3)[GlcNAc(β1,3)Gal(β1,4)]GlcNAc(β) GlcNAc(β1,6)[GlcNAc(β1,3)]Gal(β1,4)Glc(β) Fuc(α1,3)GlcNAc(β1,6)[GlcNAc(β1,3)]Gal(β) Fuc(α1,3)[Gal(β1,4)]GlcNAc(β1,6)Gal(β) GlcNAc(1,6)[Gal(β1,3)GlcNAc(β1,3)]Gal(β) Fuc(α1,6)GlcNAc(β) GlcNAc(β1,4)GlcNAc(β) Man(α1,4)GlcNAc(β1,4)GlcNAc(β) Man(α1,6)Man(α1,4)GlcNAc(β1,4)GlcNAc(β) Man(α1,3)Man(α1,4)GlcNAc(β1,4)GlcNAc(β) GlcNAc(β1,4)[GlcNAc(β1,2)]Man(α) Fuc(α1,6)[GlcNAc(β1,4)]Man(α) Gal(β1,4)GlcNAc(β1,4)[GlcNAc(β1,2)]Man(α) GlcNAc(β1,4)[Gal(β1,4)GlcNAc(β1,2)]Man(α) Man(α1,4)GlcNAcβ1,4[Fuc(α1,6)]GlcNAc(β) Gal(β1,4)GlcNAc(β) Gal(α1,3)Gal(β1,4)GlcNAc(β) Gal(β1,4)[Fuc(α1,3)]GlcNAc(β) NeuAC(α2,3)Gal(β1,4)[Fuc(α1,3)]GlcNAc(β) Gal(β1,4)GlcNAc(β1,3)Gal(β1,4)GlcNAc(β) Glc(β1,3) Glc(β) Glc(β1,2) Glc(β) Glc(β1,6) Glc(β) Glc(α1,2) Glc(α) Glc(α1,3) Glc(α) Glc(α1,4) Glc(α) Glc(α1,6) Glc(α) Ara(α1,2) Ara(α) Ara(α1,5) Ara(α) Ara(α1,2) Glc(β) Ara(α1,3) Glc(β) Ara(α1,4) Glc(β) Ara(α1,6) Glc(β) Xyl(α1,2) Man(α) Man(α1,2)Man(α) Man(α1,3)Man(α) Man(α1,6)Man(α) Gal(α1,2)Gal(α) Gal(α1,3)Gal(α) Gal(α1,4)Gal(α) Gal(α1,6)Gal(α) Gal(β1,2)Gal(β) Gal(β1,3)Gal(β) Gal(β1,6)Gal(β) NeuAc(α2,3)Gal(β1,3)GalNAc(α) NeuAc(α2,6)Gal(β1,3)GalNAc(α) NeuAc(α2,3)Gal(β1,4)GlcNAc(α) NeuAc(α2,3)Gal(β1,3)[NeuAc(α2,6)]GalNAc(α) NeuAc(α2,8)NeuAc(α2,3)Gal(β) Man(β1,4)GlcNAc(β1,4)[Fuc(α2,6)]GlcNAc(β) GlcNAc(β1,4)[Fuc(α2,6)]GlcNAc(β) Man(α1,3)Man(α1,2)Man(α1,2)Man(α) Man(α1,2)Man(α1,2)Man(α) Man(α1,3)[Man(α1,6)]Man(β1,4)GlcNAc(β) Man(β1,4)GlcNAc(β) Gal (β1,6)Gal (β1,4)Gal(β1,4)Glc (β) Gal(β1,3)Gal(β1,4)Xyl(β) Gal(α1,3)[Fuc(α1,2)]Gal(β1,4) Gal(β1,4)GlcNAc(β1,6)Gal(β) GalNAc(β1,3)Gal(β1,4)Gal(β1,4)Glc(β) GalNAc(β1,4)Gal(β1,4)Glc(β) GalNAc(α1,3)[Fuc(α1,2)]Gal(β1,4) Gal(β1,3)Gal(β1,4)Xyl(β) GlcNAc(β1,3)Gal(β1,3)GalNAc(β) GlcNAc(β1,6)Gal(β1,3)GlcNAc(β) GlcNAc(β1,3)Gal(β1,4)GlcNAc(β) GlcNAc(β1,6)[Gal(β1,3)]GalNAc(β) GlcNAc(β1,3)[GlcNAc(β1,6)]GalNAc(β) GlcNAc(β1,3)[GlcNAc(β1,6)]Gal(β) Xyl(α1,3)Glc(β) Xyl(α1,3)Xyl(α1,3)Glc(β) Gal(β1,3)GalNAc(β) Gal(β1,3)GlcNAc(β) GlcNAc(β1,3)GalNAc(β)
21 . The method of claim 1 , wherein at least some of said monosaccharides are sulfated.
22 . The method of claim 1 , wherein said sample is a serum sample or a urine sample.
23 . The method of claim 1 , wherein said addressable carbohydrate library is enzymatically synthesized.
24 . The method of claim 1 , wherein the disease is selected from the group consisting of cancer, cardiovascular diseases and transplantation.
25 . The method of claim 1 , wherein the disease, disorder or condition is selected from the group consisting of tumorogenesis, metastasis, pregnancy, vascular disease, heart disease, neurodegenerative disease, autoimmune disease, infertility, allergies and organ transplantation.
26 . The method of claim 25 , wherein said neurodegenerative disease is selected from the group consisting of Parkinson's disease, Alzheimer's disease, basal ganglia degenerative diseases, motoneuron diseases, Scrapie, spongyform encephalopathy and Creutzfeldt-Jakob's disease.
27 . The method of claim 1 , wherein said disease is an autoimmune disease and whereas said plurality of carbohydrate structures comprise Glc(β1,3)Glc(β).
28 . The method of claim 1 , wherein said disease is an autoimmune disease and whereas said plurality of carbohydrate structures comprise Man(α1,3)Man(α).
29 . The method of claim 1 , wherein said disease is an autoimmune disease and whereas said plurality of carbohydrate structures comprise GlcNAc(β1,4)GlcNAc(β).
30 . The method of claim 1 , wherein said disease is an autoimmune disease and whereas said plurality of carbohydrate structures comprise Glc(α1,4)Glc(α).
31 . The method of claim 1 , wherein said disease is cancer and whereas said plurality of carbohydrate structures comprise Gal(β1,3)GalNAc(β1,4)[Neu5Ac(α2,3)]Gal(β1,4)Glc(β).
32 . The method of claim 1 , wherein said disease is cancer and whereas said plurality of carbohydrate structures comprise Gal(β1,3)GalNAc.
33 . The method of claim 1 , wherein said disease is cancer and whereas said plurality of carbohydrate structures comprise NeuAc(α2,3)Gal(β1,3)GalNAc.
34 . The method of claim 1 , wherein said disease is cancer and whereas said plurality of carbohydrate structures comprise Gal(β1,3)[NeuAc(α2,6)]GalNAc.
35 . The method of claim 1 , wherein said disease is cancer and whereas said plurality of carbohydrate structures comprise NeuAc(α2,3)Gal(β1,3)[NeuAc(α2,6)]GalNAc.
36 . The method of claim 1 , wherein said disease is cancer and whereas said plurality of carbohydrate structures comprise Gal(β1,3)[GlcNAc(β1,6)]GalNAc.
37 . The method of claim 1 , wherein said disease is cancer and whereas said plurality of carbohydrate structures comprise Fuc(α1,2)Gal(β1,3)GalNAc.
38 . The method of claim 1 , wherein said disease is cancer and whereas said plurality of carbohydrate structures comprise GlcNAc(β1,3)Gal(β1,4)Glc(β).
39 . The method of claim 1 , wherein said disease is cancer and whereas said plurality of carbohydrate structures comprise Fuc(α1,2)Gal(β1,3)GalNAc(β1,3)Gal(α1,4)Gal(β1,4)Glc(β).
40 . The method of claim 1 , wherein said disease is cancer and whereas said plurality of carbohydrate structures comprise Neu5Ac(α2,6)GalNAc(α).
41 . The method of claim 1 , wherein said condition is transplantation and whereas said plurality of carbohydrate structures comprise Gal(α1,3)Gal(β1,4)[Fuc(α1,3)]GlcNAc(β).Join the waitlist — get patent alerts
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