Fluorescent BODIPY-based Zn(II) complex as a molecular probe for selective detection of neurofibrillary tangles in the brains of Alzheimer's disease patients. - Archive ouverte HAL Access content directly
Journal Articles Journal of the American Chemical Society Year : 2009

Fluorescent BODIPY-based Zn(II) complex as a molecular probe for selective detection of neurofibrillary tangles in the brains of Alzheimer's disease patients.

Abstract

We have developed a new fluorescent binuclear Zn(II) complex for the detection of neurofibrillary tangles (NFTs) of hyperphosphorylated tau proteins, a representative hallmark of Alzheimer's disease (AD). The probe 1 incorporates a fluorescent BODIPY unit and two Zn(II)-2,2'-dipicolylamine (Dpa) complexes as a binding site for phosphorylated amino acid residues. Using fluorescence titration to evaluate the binding and sensing properties of 1 toward several phosphorylated peptide segments derived from hyperphosphorylated tau protein, we found that 1 binds preferentially to peptides presenting phosphorylated groups at the i and i+4 positions with dissociation constants (K(d)) in the micromolar range. Fluorescence titration with an artificially prepared aggregate of the phosphorylated tau protein (p-Tau) revealed that 1 binds strongly to p-Tau (EC(50) = 9 nM). In contrast, the interactions of 1 were weaker toward artificially prepared aggregates of the nonphosphorylated tau protein (n-Tau; EC(50) = 80 nM) and Abeta(1-42) fibrils (EC(50) = 650 nM). Histological imaging of a hippocampus tissue section obtained from an AD patient revealed that 1 fluorescently visualizes deposits of NFTs and clearly discriminates between NFTs and the amyloid plaques assembled from amyloid-beta peptides, confirming our strategy toward the rational design of a molecular probe for the selective fluorescence detection of NFTs in brain tissue sections.
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Dates and versions

hal-00586940 , version 1 (18-04-2011)

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Akio Ojida, Takashi Sakamoto, Masa-Aki Inoue, Sho-Hei Fujishima, Guy Lippens, et al.. Fluorescent BODIPY-based Zn(II) complex as a molecular probe for selective detection of neurofibrillary tangles in the brains of Alzheimer's disease patients.. Journal of the American Chemical Society, 2009, 131 (18), pp.6543-8. ⟨10.1021/ja9008369⟩. ⟨hal-00586940⟩

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