Functionalized Carbohydrate Cholesterol Lowering Agent

Hypercholesterolemia constitutes a major risk factor for cardiovascular disease, the leading causeAmerica. Among the lipid-lowering therapeutics, non-systemics are frequently preferred over systemicassociated with fewer potential side effects. However, even the present non-systemics have drawbacksfor new, safe and potent cholesterol-lowering drugs. We will show that functionalization of carbohydcationic hydrophobic ligands will produce such non-systemic agents with significantly higher cholestthan cholestyramine, the currently most prescribed drug. This will involve the preparation of a sericandidates and their in vitro bile acid binding testing. Selected materials will subsequently be scrneutral sterol and bile acid excretion and their plasma cholesterol-lowering potential in hamsters.hamsters indicate that the functionalization of carbohydrates can indeed substantially increase theicholesterol-lowering efficacy. Further efficacy enhancements are required which will be achieved bycarbohydrate functionalization. The identification of a safe and potent non-systemic cholesterol-lowprovide significant therapeutic benefits to a broad section of the American public.