GLYCOSAMINOGLYCAN INHIBITORS

1 . A process for modifying the structure of chondroitin sulfate on a core protein, comprising contacting a cell that translationally produces at least one core protein having at least one attached chondroitin sulfate moiety with a selective inhibitor of a chondroitin sulfate glycosyltransferase, a chondroitin sulfate sulfotransferase, or a chondroitin sulfate phosphotransferase.

2 . The process of claim 1 , wherein the selective inhibitor of a chondroitin sulfate sulfotransferase is an inhibitor of a chondroitin sulfate O-sulfotransferase.

3 . The process of claim 2 , wherein the inhibitor of a chondroitin sulfate O-sulfotransferase inhibits the 6-OH sulfation of a galactosaminyl moiety, the 4-OH sulfation of a galactosaminyl moiety, the 2-OH sulfation of a uronic acid moiety, or a combination thereof.

4 . The process of claim 1 , wherein the inhibitor of a chondroitin sulfate glycosyltransferase inhibits the synthesis of the linkage region, the modification of the linkage region, the initiation of chondroitin sulfate synthesis, the synthesis of chondroitin sulfate, or a combination thereof.

5 . A process of inhibiting chondroitin sulfate function in a cell comprising contacting the cell with a selective modulator of a chondroitin sulfate glycosyltransferase or a modulator of a chondroitin sulfate sulfotransferase.

6 . The process of claim 5 , wherein the chondroitin sulfate function inhibited is an ability to bind a chondroitin sulfate binding lectin.

7 . The process of claim 6 , wherein the chondroitin sulfate lectin is a growth factor.

8 . The process of claim 7 , wherein the growth factor is a fibroblast growth factor (FGF), heparin binding epidermal growth factor (HB-EGF), vascular endothelial growth factor (VEGF), pleiotrophin, hepatocyte growth factor, heparin co-factor II or midkine, lamin, nuclear ribonucleoprotein, an antibody, Plasmodium falciparum lectin, annexin 4, annexin 6, PTPsigma, or endostatin.

9 . The process of claim 5 , wherein the modulator of chondroitin sulfate sulfotransferase is an inhibitor of chondroitin sulfate sulfotransferase.

10 . The process of claim 9 , wherein the inhibitor of chondroitin sulfate sulfotransferase is an inhibitor of chondroitin sulfate O-sulfotransferase.

11 . The process of claim 10 , wherein the inhibitor of chondroitin sulfate O-sulfotransferase inhibits the 6-OH sulfation of a galactosaminyl moiety, the 4-OH sulfation of a galactosaminyl moiety, the 2-OH sulfation of a uronic acid moiety, the 6-O sulfation of a galactosyl moiety, the 4-O sulfation of a galactosyl moiety, or a combination thereof.

12 . The process of claim 5 , wherein the modulator of a chondroitin sulfate sulfotransferase is a promoter of the chondroitin sulfate sulfotransferase.

13 . The process of claim 5 , wherein the modulator of a chondroitin sulfate glycosyltransferase is an inhibitor of the chondroitin sulfate glycosyltransferase.

14 . The process of claim 5 , wherein the modulator of a chondroitin sulfate glycosyltransferase is a promoter of the chondroitin sulfate glycosyltransferase.

15 . The process of claim 5 , wherein the cell is present in a human diagnosed with cancer.

16 . A process of inhibiting chondroitin sulfate function in a cell comprising contacting the cell with a selective modulator of chondroitin sulfate biosynthesis.

17 . The process of claim 16 , wherein the selective modulator of chondroitin sulfate biosynthesis inhibits chondroitin glycosylation.

18 . The process of claim 16 , wherein the selective modulator of chondroitin sulfate biosynthesis inhibits sulfation of chondroitin.

19 . The process of claim 16 , wherein the selective modulator of chondroitin sulfate biosynthesis promotes sulfation of chondroitin.

20 . The process of any of claims 16 - 19 , wherein the selective modulator of chondroitin sulfate biosynthesis has a molecular weight of less than 1,000 g/mol.

21 . A method of treating cancer comprising administering a therapeutically effective amount of a selective modulator of chondroitin sulfate glycosylation, or a selective modulator of chondroitin sulfate sulfation.

22 . The method of claim 21 , wherein the selective modulator of chondroitin sulfate biosynthesis inhibits chondroitin glycosylation.

23 . The method of claim 21 , wherein the selective modulator of chondroitin sulfate promotes chondroitin glycosylation.

24 . The method of claim 21 , wherein the selective modulator of chondroitin sulfate inhibits sulfation of chondroitin.

25 . The method of claim 21 , wherein the selective modulator of chondroitin sulfate promotes sulfation of chondroitin.

26 . The process of any of claims 21 - 25 , wherein the selective modulator of chondroitin sulfate biosynthesis has a molecular weight of less than 1,000 g/mol.

27 . A method of treating a lysosomal storage disease comprising administering a therapeutically effective amount of a selective modulator of chondroitin sulfate glycosylation, or a selective modulator of chondroitin sulfate sulfation.

28 . The method of claim 27 , wherein the lysosomal storage disease is selected from mucopolysaccharidosis.

29 . The method of either of claim 27 or 28 , wherein the selective modulator of chondroitin sulfate glycosylation is an inhibitor of chondroitin sulfate glycosylation.

30 . The method of either of claim 27 or 28 , wherein the selective modulator of chondroitin sulfate sulfation is an inhibitor of chondroitin sulfate sulfation.

31 . A method of treating an inflammatory disease comprising administering a therapeutically effective amount of a selective modulator of chondroitin sulfate glycosylation, or a selective modulator of chondroitin sulfate sulfation.

32 . The method of claim 31 , wherein, the inflammatory disease is selected from osteoarthritis.

33 . The method of either of claim 31 or 32 , wherein the selective modulator of chondroitin sulfate glycosylation is an inhibitor of chondroitin sulfate glycosylation.

34 . The method of either of claim 31 or 32 , wherein the selective modulator of chondroitin sulfate glycosylation is a promoter of chondroitin sulfate glycosylation.

35 . The method of either of claim 31 or 32 , wherein the selective modulator of chondroitin sulfate sulfation is an inhibitor of chondroitin sulfate sulfation.

36 . The method of either of claim 31 or 32 , wherein the selective modulator of chondroitin sulfate sulfation is a promoter of chondroitin sulfate sulfation.

37 . The method of any of claims 31 - 36 , wherein the selective modulator of chondroitin sulfate biosynthesis has a molecular weight of less than 1,000 g/mol.

38 . A method of treating injury to the central nervous system (CNS) comprising administering a therapeutically effective amount of a selective modulator of chondroitin sulfate glycosylation, or a selective modulator of chondroitin sulfate sulfation, wherein the modulator promotes axon regeneration.

39 . The method of claim 38 , wherein the selective modulator of chondroitin sulfate glycosylation is an inhibitor of chondroitin sulfate glycosylation.

40 . The method of claim 38 , wherein the selective modulator of chondroitin sulfate sulfation is an inhibitor of chondroitin sulfate sulfation.

41 . A process for identifying a compound that selectively modulates chondroitin sulfate biosynthesis comprising:

a. contacting a mammalian cell with the compound

b. contacting the mammalian cell and compound combination with a first labeled probe and a second labeled probe, wherein the first labeled probe binds chondroitin sulfate and the second labeled probe binds at least one glycan other than chondroitin sulfate;

c. incubating the mammalian cell, compound, the first labeled probe, and the second labeled probe;

d. collecting the first labeled probe that is bound to chondroitin sulfate;

e. collecting the second labeled probe that is bound to at least one glycan other than chondroitin sulfate;

f. detecting or measuring the amount of first labeled probe bound to chondroitin sulfate; and

g. detecting or measuring the amount of the second labeled probe bound to at least one glycan other than chondroitin sulfate.

42 . The process of claim 41 , wherein the mammalian cell is a human cervical cancer cell (HeLa).

43 . The process of claim 41 , wherein the labeled probe comprises a biotinyl moiety and the process further comprises tagging the labeled probe with streptavidin-Cy5-PE.

44 . The process of claim 41 , wherein the labeled probe comprises a fluorescent label.

45 . The process of claim 41 , wherein labeled probe is a labeled growth factor.

46 . The process of claim 45 , wherein the labeled growth factor is labeled fibroblast growth factor (FGF).

47 . A process for identifying a compound that modulates chondroitin sulfate biosynthesis comprising:

a. collecting chondroitin sulfate from a first mammalian cell of a selected type, wherein the chondroitin sulfate is sulfated oligosaccharide comprising galactosaminyl groups, and glucuronic acid groups;

b. cleaving the chondroitin sulfate into a plurality of disaccharide component parts;

c. measuring:

i. the amount of chondroitin sulfate disaccharides produced by the first mammalian cell,

ii. the amount of 6-OH sulfation of the galactosaminyl groups, the 4-OH sulfation of the galactosaminyl groups, the 2-OH sulfation of the uronic acid groups, or a combination thereof of the chondroitin sulfate,

iii. the pattern of sulfation; or

iv. a combination thereof; and

d. contacting and incubating a second mammalian cell of the selected type with the compound;

e. collecting modified chondroitin sulfate from the second mammalian cell, wherein the modified chondroitin sulfate is sulfated oligosaccharide comprising galactosaminyl groups, and glucuronic acid groups;

f. cleaving the modified chondroitin sulfate into a plurality of disaccharide component parts;

g. measuring:

i. the amount of chondroitin sulfate disaccharides produced by the second mammalian cell,

ii. the amount of 6-OH sulfation of the galactosaminyl groups, the 4-OH sulfation of the galactosaminyl groups, the 2-OH sulfation of the uronic acid groups, or a combination thereof of the modified chondroitin sulfate,

iii. the pattern of sulfation; or

iv. a combination thereof; and

h. comparing:

i. the amounts of chondroitin sulfate disaccharides produced by the first and second mammalian cells,

ii. the amounts of 6-OH sulfation of the galactosaminyl groups, the 4-OH sulfation of the galactosaminyl groups, the 2-OH sulfation of the uronic acid groups, pattern of sulfation, or a combination thereof of the chondroitin sulfate and the modified chondroitin sulfate,

iii. the pattern of sulfation; or

iv. a combination thereof.

48 . A process for modifying the structure of chondroitin sulfate on a core protein, comprising contacting a cell that translationally produces at least one core protein having at least one attached chondroitin sulfate moiety with a selective inhibitor of a chondroitin sulfate glycosyltransferase, a chondroitin sulfate sulfotransferase, or a chondroitin sulfate phosphotransferase.

49 . A process for modifying the structure of keratan sulfate on a core protein, comprising contacting a cell that translationally produces at least one core protein having at least one attached keratan sulfate moiety with a selective inhibitor of a keratan sulfate glycosyltransferase, a keratan sulfate sulfotransferase, or a keratan sulfate phosphotransferase.

50 . A process for modifying the structure of dermatan sulfate on a core protein, comprising contacting a cell that translationally produces at least one core protein having at least one attached dermatan sulfate moiety with a selective inhibitor of a dermatan sulfate glycosyltransferase, a dermatan sulfate sulfotransferase, or a dermatan sulfate phosphotransferase.

51 . A process of modulating chondroitin sulfate biosynthesis in a cell comprising contacting the cell with a selective modulator of chondroitin sulfate biosynthesis, wherein the selective modulator is optionally (i) cellularly active, (ii) a non-carbohydrate small molecule having a molecular weight of less than 1000 g/mol, (iii) an inhibitor of chondroitin sulfate biosynthesis, and/or (iv) an indirect modulator (e.g., inhibitor) of chondroitin sulfate biosynthesis.

52 . The process of claim 51 , wherein the selective modulator of chondroitin sulfate biosynthesis alters or disrupts the chain length of chondroitin sulfate compared to endogenous chondroitin sulfate by at least 5%.

53 . The process of claim 51 , wherein the selective modulator of chondroitin sulfate biosynthesis alters or disrupts the concentration of chondroitin sulfate compared to endogenous chondroitin sulfate by at least 5%.

54 . The process of claim 51 , wherein the selective modulator of chondroitin sulfate biosynthesis alters or disrupts the 2-O sulfation of chondroitin sulfate compared to endogenous chondroitin sulfate by at least 5%.

55 . The process of claim 51 , wherein the selective modulator of chondroitin sulfate biosynthesis alters or disrupts the 4-O sulfation of chondroitin sulfate compared to endogenous chondroitin sulfate by at least 5%.

56 . The process of claim 51 , wherein the selective modulator of chondroitin sulfate biosynthesis alters or disrupts the 6-O sulfation of chondroitin sulfate compared to endogenous chondroitin sulfate by at least 5%.

57 . The process of claim 51 , wherein the selective modulator of chondroitin sulfate biosynthesis alters the ratio of 4-O sulfation to 6-O sulfation to below 6.3 to 1.

58 . The process of claim 51 , wherein the selective modulator of chondroitin sulfate biosynthesis alters the ratio of 6-O sulfation to 2-O sulfation to below 0.16 to 1.

59 . The process of claim 51 , wherein the selective modulator is a direct modulator (e.g., inhibitor) of chondroitin sulfate biosynthesis

60 . A process of modulating dermatan sulfate biosynthesis in a cell comprising contacting the cell with a selective modulator of dermatan sulfate biosynthesis, wherein the selective modulator is optionally (i) cellularly active, (ii) a non-carbohydrate small molecule having a molecular weight of less than 1000 g/mol, (iii) an inhibitor of dermatan sulfate biosynthesis, and/or (iv) an indirect modulator (e.g., inhibitor) of dermatan sulfate biosynthesis.

61 . The process of claim 60 , wherein the selective modulator of dermatan sulfate biosynthesis alters the ratio of 2-O sulfation to 4-O sulfation to below 0.13 to 1.

62 . The process of claim 60 , wherein the selective modulator of dermatan sulfate biosynthesis alters the ratio of 2-O sulfation to 6-O sulfation to below 1.44 to 1.

63 . The process of claim 60 , wherein the selective modulator of dermatan sulfate biosynthesis alters the ratio of 4-O sulfation to 6-O sulfation to below 11.4 to 1.

64 . The process of claim 60 , wherein the selective modulator of dermatan sulfate biosynthesis alters the ratio of 4-O sulfation to 2-O sulfation to below 7.9 to 1.

65 . The process of claim 60 , wherein the selective modulator of dermatan sulfate biosynthesis alters the ratio of 6-O sulfation to 2-O sulfation to below 0.7 to 1.

66 . The process of claim 60 , wherein the selective modulator of dermatan sulfate biosynthesis alters the ratio of 6-O sulfation to 4-O sulfation to below 0.09 to 1.

67 . The process of claim 60 , wherein the selective modulator is a direct modulator (e.g., inhibitor) of dermatan sulfate biosynthesis