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 (Abeta) 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-Abeta IgGs to Abeta fibrils. A molecular surface coating with 3,6-diamino acridine was able to inhibit 76+/-10% of the binding of an anti-Abeta IgG to Abeta 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.
Inbar
Petra
P
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, MC 0358, La Jolla, CA 92093-0358, USA.
Yang
Jerry
J
D000166:Acridines / Q000737:chemistry*; D000682:Amyloid / Q000737:chemistry*; D052160:Benzothiazoles; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000737:chemistry; D015394:Molecular Structure; D011370:Proflavine; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D013499:Surface Properties; D013844:Thiazoles / Q000737:chemistry*
D000166:Acridines; D000682:Amyloid; D052160:Benzothiazoles; D007074:Immunoglobulin G; D011506:Proteins; D013844:Thiazoles; C009462:thioflavin T; D011370:Proflavine