title: Modulation of Amyloid Aggregates into Nontoxic Coaggregates by Hydroxyquinoline Appended Polyfluorene.
abstract: Inhibitory modulation toward de novo protein aggregation is likely to be a vital and promising therapeutic strategy for understanding the molecular etiology of amyloid related diseases such as Alzheimer's disease (AD). The building up of toxic oligomeric and fibrillar amyloid aggregates in the brain plays host to a downstream of events, causing damage to axons, dendrites, synapses, signaling, transmission, and finally cell death. Herein, we introduce a novel conjugated polymer (CP), hydroxyquinoline appended polyfluorene (PF-HQ), which has a typical "amyloid like" surface motif and exhibits inhibitory modulation effect on amyloid β (Aβ) aggregation. We delineate inhibitory effects of PF-HQ based on Thioflavin T (ThT) fluorescence, atomic force microscopy (AFM), circular dichroism (CD), and Fourier transform infrared (FTIR) studies. The amyloid-like PF-HQ forms nano coaggregates by templating with toxic amyloid intermediates and displays improved inhibitory impacts toward Aβ fibrillation and diminishes amyloid cytotoxicity. We have developed a CP based modulation strategy for the first time, which demonstrates beneficiary amyloid-like surface motif to interact efficiently with the protein, the pendant side groups to trap the toxic amyloid intermediates as well as optical signal to acquire the mechanistic insight.
authors.affiliation: Department of Chemistry, ‡Department of Bioscience and Bioengineering, and §Center for Nanotechnology, Indian Institute of Technology Guwahati , Guwahati, 781039 Assam, India.
authors.forename: Sayan Roy
authors.initials: SR
authors.lastname: Chowdhury
authors.affiliation: Department of Chemistry, ‡Department of Bioscience and Bioengineering, and §Center for Nanotechnology, Indian Institute of Technology Guwahati , Guwahati, 781039 Assam, India.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Agarwal
authors.affiliation: Department of Chemistry, ‡Department of Bioscience and Bioengineering, and §Center for Nanotechnology, Indian Institute of Technology Guwahati , Guwahati, 781039 Assam, India.
authors.forename: Niranjan
authors.initials: N
authors.lastname: Meher
authors.affiliation: Department of Chemistry, ‡Department of Bioscience and Bioengineering, and §Center for Nanotechnology, Indian Institute of Technology Guwahati , Guwahati, 781039 Assam, India.
authors.forename: Balakrishnan
authors.initials: B
authors.lastname: Muthuraj
authors.affiliation: Department of Chemistry, ‡Department of Bioscience and Bioengineering, and §Center for Nanotechnology, Indian Institute of Technology Guwahati , Guwahati, 781039 Assam, India.
authors.forename: Parameswar Krishnan
authors.initials: PK
authors.lastname: Iyer
mesh_terms: D000544:Alzheimer Disease; D020816:Amino Acid Motifs; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D005449:Fluorenes / Q000737:chemistry* / Q000494:pharmacology*; D006912:Hydroxyquinolines / Q000737:chemistry*; D010446:Peptide Fragments; D066263:Protein Aggregation, Pathological / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects
chemical_list: D000682:Amyloid; D005449:Fluorenes; D006912:Hydroxyquinolines; D010446:Peptide Fragments
keywords: Alzheimer’s disease; amyloid β; conjugate polymeric material; neurodegenerative diseases; oligomeric and fibrillar amyloid aggregates; polymer−protein coaggregates