Effective Amyloid Defibrillation by Polyhydroxyl-Substituted Squaraine Dyes.

With an objective to develop β-amyloid destabilizing agents, we have investigated the interactions of a few water-soluble near-infrared (NIR)-absorbing squaraine dyes 1-3 with lysozyme and its amyloid aggregates through photophysical and biophysical techniques. These dyes exhibited strong interactions with lysozyme and β-amyloids in addition to serum albumins as evidenced by the absorption and emission changes. The interactions were found to be spontaneous with association constant values in the range of approximately 10(4)-10(5)  m(-1), as confirmed through half-reciprocal analysis and isothermal calorimetric measurements. Uniquely, such effective interactions of the dyes have led to the complete disassembly of the β-amyloid fibrillar structures to form spherical particles approximately 350 nm in size, as confirmed through photophysical, thioflavin assay, circular dichroism (CD), atomic force microscopy (AFM), TEM, and selected-area electron diffraction (SAED) techniques. These results demonstrate that the squaraine dyes 1-3 under investigation act as effective protein-labelling and destabilizing agents of the protein amyloidogenesis.