Effective Amyloid Defibrillation by Polyhydroxyl‐Substituted Squaraine Dyes

Abstract

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.

Vitamin k3 inhibits protein aggregation: Implication in the treatment of amyloid diseases

“…As shown in Fig. 4, HEWL sample alone incubated for 120 hours formed large, branched fibrils which are characteristic feature of amyloids41. Samples of HEWL in presence of vitamin k3 (50 and 100 μM) showed no fibrillar aggregate.…”

Nanoparticle-conjugated nutraceuticals exert prospectively palliative of amyloid aggregation

“…However, unmodified curcumin has poor sensitivity, specifically it is difficult to penetrate the blood-brain barrier, researchers choosing alternatively, the polyhydroxyl substituted squaraine dyes 1-3 under investigation act as effective protein-labeling and destabilizing agents of the protein amyloidogenesis as well. 97 Undeniably, AuNPs were more expensive than silver (Ag). Recently, fluorescence quenching by lipid encased Ag nanoparticle is performed to discover that membrane-inserted Aβ oligomers have a preferred molecular orientation.…”

Helicity Control in the Aggregation of Achiral Squaraine Dyes in Solution and Thin Films

“…Previous studies on squaraine dyes have focused often on nitrogen‐based heterocycles [4, 16, 37–39] or N , N ‐dialkylaminoaryl substituted derivatives [6, 12, 40] since the formation of the squaraine unit succeeds only when the nucleophilicity of the reagent used for the condensation reaction with squaric acid is sufficiently high [41] . Squaraine dyes that comprise para ‐hydroxy substitution have received less attention [42–44] . Replacement of the tertiary amine group in the squaraine precursor by a hydroxyl group renders the resulting squaraine dye an acid, which readily reacts with traces of water present in organic solvent [41] …”

“…[41] Squaraine dyes that comprise parahydroxy substitution have received less attention. [42][43][44] Replacement of the tertiary amine group in the squaraine precursor by ah ydroxyl group renders the resulting squaraine dye an acid, which readily reacts with traces of water present in organic solvent. [41] Both presented dyes combine squaraine motifs with amide functionalised side chains.T he combination of amide functionalised side chains and planar motifs such as the benzene-1,3,5tricarboxamide, [45] porphyrin [46] or naphthalene diimide( NDI) [47] is well-described in the literature to induce the formation of supramolecular aggregates.T he successful attachment of amide substituents to the squaraine motif in order to induce supramolecular aggregation has so far been reportedo nly once for an achiral squarained ye derivative.…”