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

Akio Ojida, Takashi Sakamoto, Masa Aki Inoue, Sho Hei Fujishima, Guy Lippens, Itaru Hamachi

研究成果: ジャーナルへの寄稿記事

122 引用 (Scopus)

抄録

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 (Kd) 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 (EC50 ) 9 nM). In contrast, the interactions of 1 were weaker toward artificially prepared aggregates of the nonphosphorylated tau protein (n-Tau; EC50 ) 80 nM) and Aγ1-42 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-γ peptides, confirming our strategy toward the rational design of a molecular probe for the selective fluorescence detection of NFTs in brain tissue sections.

元の言語英語
ページ(範囲)6543-6548
ページ数6
ジャーナルJournal of the American Chemical Society
131
発行部数18
DOI
出版物ステータス出版済み - 5 13 2009

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Molecular Probes
tau Proteins
Neurofibrillary Tangles
Brain Diseases
Brain
Alzheimer Disease
Proteins
Peptides
Fluorescence
Titration
Amyloid
Dissociative Disorders
Tissue
Amyloid Plaques
Binding sites
Amino acids
Hippocampus
Deposits
Binding Sites
4,4-difluoro-4-bora-3a,4a-diaza-s-indacene

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

これを引用

Fluorescent BODIPY-based Zn(II) complex as a molecular probe for selective detection of neurofibrillary tangles in the brains of alzheimer's disease patients. / Ojida, Akio; Sakamoto, Takashi; Inoue, Masa Aki; Fujishima, Sho Hei; Lippens, Guy; Hamachi, Itaru.

:: Journal of the American Chemical Society, 巻 131, 番号 18, 13.05.2009, p. 6543-6548.

研究成果: ジャーナルへの寄稿記事

Ojida, Akio ; Sakamoto, Takashi ; Inoue, Masa Aki ; Fujishima, Sho Hei ; Lippens, Guy ; Hamachi, Itaru. / 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 ; 巻 131, 番号 18. pp. 6543-6548.
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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 (Kd) 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 (EC50 ) 9 nM). In contrast, the interactions of 1 were weaker toward artificially prepared aggregates of the nonphosphorylated tau protein (n-Tau; EC50 ) 80 nM) and Aγ1-42 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-γ 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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