Sci. Aging Knowl. Environ., 3 November 2004
Harnessing Chaperones to Generate Small-Molecule Inhibitors of Amyloid Aggregation
Jason E. Gestwicki, Gerald R. Crabtree, and Isabella A. Graefhttp://sageke.sciencemag.org/cgi/content/abstract/2004/44/or19
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 -amyloid (A) aggregation, we synthesized small molecules that increase their steric bulk by binding to chaperones but also have a moiety available for interaction with A. This strategy yields potent inhibitors of A aggregation and could lead to therapeutics for Alzheimer's disease and other forms of neurodegeneration.
Science of Aging Knowledge Environment. ISSN 1539-6150