Zinspy Sensors with Enhanced Dynamic Range for Imaging Neuronal Cell Zinc Uptake and Mobilization

Autor: Rodney P. Feazell, Jubin W. Ryu, Stephen J. Lippard, Jacek Jaworski, Elizabeth M. Nolan, Morgan Sheng
Rok vydání: 2006
Předmět:
Zdroj: Journal of the American Chemical Society. 128:15517-15528
ISSN: 1520-5126
0002-7863
DOI: 10.1021/ja065759a
Popis: 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.
Databáze: OpenAIRE