title: A High Affinity Red Fluorescence and Colorimetric Probe for Amyloid β Aggregates.
abstract: A major challenge in the Alzheimer's disease (AD) is its timely diagnosis. Amyloid β (Aβ) aggregates have been proposed as the most viable biomarker for the diagnosis of AD. Here, we demonstrate hemicyanine-based benzothiazole-coumarin (TC) as a potential probe for the detection of highly toxic Aβ42 aggregates through switch-on, enhanced (~30 fold) red fluorescence (Emax = 654 nm) and characteristic colorimetric (light red to purple) optical outputs. Interestingly, TC exhibits selectivity towards Aβ42 fibrils compared to other abnormal protein aggregates. TC probe show nanomolar binding affinity (Ka = 1.72 × 10(7) M(-1)) towards Aβ42 aggregates and also displace ThT bound to Aβ42 fibrils due to its high binding affinity. The Aβ42 fibril-specific red-shift in the absorption spectra of TC responsible for the observed colorimetric optical output has been attributed to micro-environment change around the probe from hydrophilic-like to hydrophobic-like nature. The binding site, binding energy and changes in optical properties observed for TC upon interaction with Aβ42 fibrils have been further validated by molecular docking and time dependent density functional theory studies.
authors.affiliation: Bioorganic Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O., Bengaluru 560064, Karnataka, India.
authors.forename: K
authors.initials: K
authors.lastname: Rajasekhar
authors.affiliation: Bioorganic Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O., Bengaluru 560064, Karnataka, India.
authors.forename: Nagarjun
authors.initials: N
authors.lastname: Narayanaswamy
authors.affiliation: Division of Theoretical Chemistry and Biology, School of Biotechnology, KTH Royal Institute of Technology, S-106 91 Stockholm, Sweden.
authors.forename: N Arul
authors.initials: NA
authors.lastname: Murugan
authors.affiliation: Division of Theoretical Chemistry and Biology, School of Biotechnology, KTH Royal Institute of Technology, S-106 91 Stockholm, Sweden.
authors.forename: Guanglin
authors.initials: G
authors.lastname: Kuang
authors.affiliation: Division of Theoretical Chemistry and Biology, School of Biotechnology, KTH Royal Institute of Technology, S-106 91 Stockholm, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Ågren
authors.affiliation: Bioorganic Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P.O., Bengaluru 560064, Karnataka, India.
authors.forename: T
authors.initials: T
authors.lastname: Govindaraju
mesh_terms: D065638:Absorption, Radiation; D000544:Alzheimer Disease / Q000175:diagnosis*; D000682:Amyloid / Q000032:analysis*; D016229:Amyloid beta-Peptides / Q000032:analysis*; D052160:Benzothiazoles; D003124:Colorimetry / Q000379:methods*; D005456:Fluorescent Dyes / Q000032:analysis / Q000737:chemistry; D005470:Fluorometry / Q000379:methods*; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010446:Peptide Fragments / Q000032:analysis*; D066263:Protein Aggregation, Pathological; D013844:Thiazoles / Q000032:analysis / Q000737:chemistry
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); C009462:thioflavin T