title: Benzothiazole-Based Neutral Ratiometric Fluorescence Sensor for Amyloid Fibrils.
abstract: Early detection of amyloid fibrils is very important for the timely diagnosis of several neurological diseases. Thioflavin-T (ThT) is a gold standard fluorescent probe for amyloid fibrils and has been used for the last few decades. However, due to its positive charge, ThT is incapable of crossing the blood-brain barrier and cannot be used for in vivo imaging of fibrils. In the present work, we synthesized a neutral ThT derivative, 2-[2'-Me,4'-(dimethylamino)phenyl]benzothiazole (2Me-DABT), which showed a strong affinity towards the amyloid fibrils. On association with the amyloid fibrils, 2Me-DABT not only showed a large increase in its emission intensity, but also, unlike ThT, a large blueshift in its emission spectrum was observed. Thus, unlike ThT, 2Me-DABT is a potential candidate for the ratiometric sensor of the amyloid fibrils. Detailed photophysical properties of 2Me-DABT in amyloid fibrils and different solvent media were studied to understand its sensory activity. Fluorescence resonance energy transfer (FRET) studies suggested that the sites of localization for ThT and 2Me-DABT in amyloid fibrils are not same and their average distance of separation in amyloid fibrils was determined. The experimental data was nicely supported by molecular docking studies, which confirmed the binding of 2Me-DABT in the inner core of the amyloid fibrils.
authors.affiliation: Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India.
authors.forename: Aruna K
authors.initials: AK
authors.lastname: Mora
authors.affiliation: Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India.
authors.forename: Sushant
authors.initials: S
authors.lastname: Murudkar
authors.affiliation: Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India.|Cardomom Planters Association College, Bodinayakanur, Tamil Nadu, India.
authors.forename: A
authors.initials: A
authors.lastname: Alamelu
authors.affiliation: Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India.
authors.forename: Prabhat K
authors.initials: PK
authors.lastname: Singh
authors.affiliation: Bio-organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India.
authors.forename: Subrata
authors.initials: S
authors.lastname: Chattopadhyay
authors.affiliation: Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400 085, India. snath@barc.gov.in, sukhendunath@yahoo.co.in.
authors.forename: Sukhendu
authors.initials: S
authors.lastname: Nath
mesh_terms: D000682:Amyloid / Q000032:analysis*; D052160:Benzothiazoles / Q000737:chemistry*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D012997:Solvents / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry*
chemical_list: C000627178:2-(2'-Me,4'-(dimethylamino)phenyl)benzothiazole; D000682:Amyloid; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D012997:Solvents; D013844:Thiazoles; C009462:thioflavin T
keywords: amyloid fibrils; biosensors; fluorescent probes; thioflavin-T; time-resolved spectroscopy