Effective Amyloid Defibrillation by Polyhydroxyl-Substituted Squaraine Dyes
Dhanya T Jayaram1, Balaraman H Shankar1, Danaboyina Ramaiah2,3
1Photosciences and Photonics Section, Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Trivandrum 695019, Kerala, India.
New squaraine dyes effectively interact with and destabilize beta-amyloid aggregates. These near-infrared absorbing compounds show potential for protein amyloidogenesis research and diagnostics.
Area of Science:
- Biophysical Chemistry
- Materials Science
- Neuroscience
Background:
- Protein misfolding and aggregation into amyloid fibrils are implicated in various neurodegenerative diseases.
- Developing agents to destabilize amyloid structures is a key therapeutic and diagnostic challenge.
Purpose of the Study:
- To investigate the interaction of water-soluble near-infrared (NIR)-absorbing squaraine dyes with lysozyme and beta-amyloid aggregates.
- To evaluate the potential of these dyes as protein-labelling and amyloid destabilizing agents.
Main Methods:
- Photophysical techniques (absorption and emission spectroscopy)
- Biophysical techniques including isothermal calorimetry and half-reciprocal analysis
- Structural analysis using thioflavin assay, circular dichroism (CD), atomic force microscopy (AFM), transmission electron microscopy (TEM), and selected-area electron diffraction (SAED)
Main Results:
- Squaraine dyes 1-3 demonstrated strong, spontaneous interactions with lysozyme and beta-amyloids (association constants ~10^4-10^5 M^-1).
- These interactions led to the complete disassembly of beta-amyloid fibrillar structures into spherical particles (~350 nm).
- Dyes were confirmed as effective protein-labelling agents.
Conclusions:
- Water-soluble NIR-absorbing squaraine dyes are potent agents for destabilizing beta-amyloid aggregates.
- These squaraine dyes show promise as tools for studying and potentially treating protein amyloidogenesis.
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