MODIFIED AND DERIVATIZED ß-GLUCAN COMPOUNDS, COMPOSITIONS, AND METHODS
Modified and/or derivativized β-glucans with an enhanced capacity to modulate human immune response as compared to the parent, unmodified and/or underivatized β-glucans are demonstrated.
1 - 41 . (canceled)
42 . A composition comprising a chemically modified beta 1,3 linked glucose polymer of at least 3 glucose residues having a backbone with at least one glucose residue linked to the backbone via a beta 1,6 linkage resulting in a sidechain, wherein at least one glucose residue containing a vicinal diol within the polymer has been transformed into a substituted morpholine or [1,4]-oxazepane via periodate oxidation and reductive amination with a protein.
43 . The composition of claim 42 wherein protein is bovine serum albumin.
44 . The composition f claim 42 wherein the protein comprises an antibody.
45 . The composition of claim 44 herein the antibody is used as a tumor therapy.
46 . The composition of claim 45 wherein the antibody is cetuximab.
47 . A composition comprising a chemically modified beta 1,3 linked glucose polymer of at least 3 glucose residues having at least one hydroxyl group of the polymer linked to a second amine via an imidocarbamate linkage formed via cyanogen bromide or 1-cyano-4-dimethylaminopyridinium tetrafluoroborate.
48 . The composition of claim 47 wherein the second amine is a peptide or protein.
49 . The composition of claim 48 wherein the protein is bovine serum albumin.
50 . The composition of claim 47 wherein the protein is an antibody.
51 . A composition comprising a chemically modified beta 1,3 linked glucose polymer of at least 3 glucose residues wherein at least one hydroxyl group of the polymer is alkylated with a HBr salt of 1-amino-3-bromopropane resulting in a primary propyl amine.
52 . The composition of claim 51 wherein the primary amine is reductively aminated with an aldehyde.
53 . The composition of claim 52 wherein the aldehyde is a reducing sugar.
54 . The composition of claim 53 wherein the reducing sugar is glucose, galactose, mannose, maltose, melbiose, cellobiose, maltopentaose, N-acetylglucosamine, or lactose.
55 . The composition of claim 51 wherein the primary amine has been transformed into one of a substituted sulfonamide, amide, urea, or thiourea.
56 . The composition of claim 55 wherein the substitution on the sulfonamide is methyl, 2-propyl, 1-propyl, isobutyl, cyclohexyl, benzyl, phenyl, or p-toluenyl.
57 . The composition of claim 55 in which the amine is reacted with benzenedisulfonyl chloride resulting in a crosslinked glucan.
58 . A composition comprising a chemically modified beta 1,3 linked glucose polymer of at least 3 glucose residues in which at least one primary hydroxyl group of the polymer is oxidized to a carboxylic acid.
59 . The composition of claim 58 wherein the carboxylic acid is converted to a substituted amide by coupling with an amine.
60 . The composition of claim 59 in which the amine comprises one of benzyl amine, 1,3-diaminopropane, serotonin, tryptamine, histamine, 4-aminomethylpyridine, R-(−)-2-phenyl glycinol L-(−)-2-amino-3-phenyl-1-propanol, furfuryl amine, or 1-(3-aminopropyl) imidazole.