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Zinspy Sensors with Enhanced Dynamic Range for Imaging Neuronal Cell Zinc Uptake and Mobilization
Open accessAbstract
Thiophene moieties were incorporated into previously described Zinspy (ZS) fluorescent Zn(II) sensor motifs (Nolan, E. M.; Lippard, S. J. Inorg. Chem. 2004, 43, 8310-8317) to provide enhanced fluorescence properties, low-micromolar dissociation constants for Zn(II), and improved Zn(II) selectivity. Halogenation of the xanthenone and benzoate moieties of the fluorescein platform systematically modulates the excitation and emission profiles, pH-dependent fluorescence, Zn(II) affinity, and Zn(II) complexation rates, offering a general strategy for tuning multiple properties of xanthenone-based metal ion sensors. Extensive biological studies in cultured cells and primary neuronal cultures demonstrate 2-{6-hydroxy-3-oxo-4,5-bis[(pyridin-2-ylmethylthiophen-2-ylmethylamino)methyl]-3H-xanthen-9-yl}benzoic acid (ZS5) to be a versatile imaging tool for detecting Zn(II) in vivo. ZS5 localizes to the mitochondria of HeLa cells and allows visualization of glutamate-mediated Zn(II) uptake in dendrites and Zn(II) release resulting from nitrosative stress in neurons.
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Cited by
Synthetic fluorescent sensors for studying the cell biology of metals
Domaille, D. W., Que, E. L., & Chang, C. J. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.69 · Cited by 1,081
Small-Molecule Fluorescent Sensors for Investigating Zinc Metalloneurochemistry
Nolan, E. M., & Lippard, S. J. (2009) · Accounts of Chemical Research · doi:10.1021/ar8001409 · Cited by 620
Self-citationZhao, Y., Zhang, X.-B., Han, Z.-X., Qiao, L., Li, C.-Y., Jian, L.-X., Shen, G.-L., & Yu, R.-Q. (2009) · Analytical Chemistry · doi:10.1021/ac901127n · Cited by 455
Metadata
- Authors
- Nolan, E. M., Ryu, J. W., Jaworski, J., Feazell, R. P., Sheng, M., & Lippard, S. J.
- Venue
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Published
- 2006-11-08
- Volume
- 128
- Issue
- 48
- Pages
- 15517-15528
- ISSN
- 0002-7863 (ISSN-L)
- 1520-5126
- OpenAlex
- W2081895000
- Cited by
- 240
- References
- 0
- FWCI
- 6.95
- Type
- journal article
- Language
- en
- Open access
- green
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- Nolan, E. M., Ryu, J. W., Jaworski, J., Feazell, R. P., Sheng, M., & Lippard, S. J. (2006). Zinspy Sensors with Enhanced Dynamic Range for Imaging Neuronal Cell Zinc Uptake and Mobilization. Journal of the American Chemical Society. https://doi.org/10.1021/ja065759a
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