Sci. Aging Knowl. Environ., 3 November 2004
Vol. 2004, Issue 44, p. or19


Harnessing Chaperones to Generate Small-Molecule Inhibitors of Amyloid {beta} Aggregation

Jason E. Gestwicki, Gerald R. Crabtree, and Isabella A. Graef

Abstract: Science 306, 865-869 (2004).

Protein aggregation is involved in the pathogenesis of neurodegenerative diseases and hence is considered an attractive target for therapeutic intervention. However, protein-protein interactions are exceedingly difficult to inhibit. Small molecules lack sufficient steric bulk to prevent interactions between large peptide surfaces. To yield potent inhibitors of {beta}-amyloid (A{beta}) aggregation, we synthesized small molecules that increase their steric bulk by binding to chaperones but also have a moiety available for interaction with A{beta}. This strategy yields potent inhibitors of A{beta} aggregation and could lead to therapeutics for Alzheimer's disease and other forms of neurodegeneration.

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Science of Aging Knowledge Environment. ISSN 1539-6150