Method of inhibiting the advanced glycosylation of proteins using 1,2-disubstituted-benzimidazoles
AssigneesThe Rockefeller University, Alteon Inc.
InventorsPeter C. Ulrich, Anthony Cerami, Dilip R. Wagle
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Abstract
The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging). Accordingly, composition is disclosed which comprises 1,2-disubstituted benzimidazoles capable of inhibiting the formation of advanced glycosylation endproducts of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
Claims11
A method for inhibiting the advanced glycosylation of a target protein comprising contacting the target protein with an effective amount of composition comprising a compound selected from the group consisting of compounds of the formula ##STR3## wherein R.sub.1 is hydrogen or an amino group;
- R.sub.2 is an amino group or a guanidino group when R.sub.1 is hydrogen;
- or R.sub.2 is an amino group when R.sub.1 is an amino group;
- R.sub.3 and R.sub.4 are independently hydrogen, hydroxy, a lower alkyl group, a lower alkoxy group, or an aryl group;
- and their biologically or pharmaceutically acceptable acid or alkali addition salts;
- and mixtures thereof, and a carrier therefor.
A method for treating an animal to inhibit the formation of advanced glycosylation endproducts of a target protein within said animal, said method comprising administering an effective amount of a pharmaceutical composition, said pharmaceutical composition comprising a compound selected from the group consisting of compounds of the formula ##STR4## wherein R.sub.1 is hydrogen or an amino group;
- R.sub.2 is an amino group or a guanidino group when R.sub.1 is hydrogen;
- or R.sub.2 is an amino group when R.sub.1 is an amino group;
- R.sub.3 and R.sub.4 are independently hydrogen, hydroxy, a lower alkyl group, a lower alkoxy group, or an aryl group;
- and their biologically or pharmaceutically acceptable acid or alkali addition salts;
- and mixtures thereof, and a carrier therefor.
A method of inhibiting the discoloration of teeth resulting from non-enzymatic browning in the oral cavity which comprises administration of an amount effective to inhibit the formation of advanced glycosylation endproducts of a composition comprising a compound selected from the group consisting of compounds of the formula ##STR5## wherein R.sub.1 is hydrogen or an amino group;
- R.sub.2 is an amino group or a guanidino group when R.sub.1 is hydrogen;
- or R.sub.2 is an amino group when R.sub.1 is an amino group;
- R.sub.3 and R.sub.4 are independently hydrogen, hydroxy, a lower alkyl group, a lower alkoxy group, or an aryl group;
- and their biologically or pharmaceutically acceptable acid or alkali addition salts;
- and mixtures thereof, and a carrier therefor.
Dependencies are inferred from the claim text.