Inhibiting protein-amyloid interactions with small molecules: A surface chemistry approach

This paper presents a surface-based approach to inhibit the binding of proteins to Alzheimer's-related beta-amyloid (A beta) fibrils with small molecules. It reports the idea of using an intracellular, disease-related fibril as a material whose surface can be coated with small molecules. Using an ELISA-based assay, molecular surface coatings with thioflavin T are shown to inhibit 65 +/- 10% of the binding of two different anti-A beta IgGs to A beta fibrils. A molecular surface coating with 3,6-diamino acridine was able to inhibit 76 +/- 10%, of the binding of an anti-A beta IgG to A beta fibrils. Maximal inhibition of these protein-amyloid interactions appears in the low to mid-micromolar range of small molecule. This demonstration that molecular surface coatings can be used to attenuate the interaction of proteins with these fibrils suggests a potentially new strategy for therapeutics in neurodegenerative amyloid diseases. (c) 2005 Elsevier Ltd. All rights reserved.