Methods for alleviating deleterious effects of 3-deoxyglucosone
AssigneeFox Chase Cancer Center
InventorsTruman R. Brown, Francis Kappler
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Abstract
Disclosed is a class of compounds which inhibit the enzymatic conversion of fructose-lysine into fructose-lysine-3-phosphate in an ATP dependent reaction in a newly discovered metabolic pathway. According to the normal functioning on this pathway, fructose-lysine-3-phosphate (FL3P) is broken down to form free lysine, inorganic phosphate and 3-deoxyglucosone (3DG), the latter being a reactive protein modifying agent. 3DG can be detoxified by reduction to 3-deoxyfructose (3DF), or it can react with endogenous proteins to form advanced glycation end-product modified proteins (AGE-proteins) Also disclosed are therapeutic methods of using such inhibitors to alleviate deleterious effects of 3DG.
Claims12
-4. (canceled)
A method of alleviating the deleterious effects of aging in a patient in need thereof, said effects being due to the production of 3DG by the enzymatic conversion of fructose-lysine (FL) to fructose-lysine-3-phosphate (FL3P), said method comprising administering to said patient an effective amount of an inhibitor or of said enzymatic conversion of FL to FL3P, said inhibitor being selected from the group consisting of sorbitollysine, mannitollysine, galactitollysine, 3-O-methyl sorbitollysine, meglumine and the pharmaceutically acceptable salts thereof.
A method of reducing advanced glycation end products (AGEs) in living tissue, said AGEs being formed by the chemical modification of protein by 3-deoxyglucosome (3DG) produced by the enzymatic conversion of fructose-lysine (FL) to fructose-lysine-3-phosphate (FL3P), said method comprising delivering to said tissue an effective amount of an inhibitor of said enzymatic conversion of FL to FL3P, said inhibitor being elected from the group consisting of sorbitollysine, mannitollysine, galactitollysine, 3-O-methyl sorbitollysine, meglumine and the pharmaceutically acceptable salts thereof.
Dependencies are inferred from the claim text.