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  Microscopic Visualization of Metabotropic Glutamate Receptors on the Surface of Living Cells Using Bifunctional Magnetic Resonance Imaging Probes

Mishra, A., Mishra, R., Gottschalk, S., Pal, R., Sim, N., Engelmann, J., et al. (2014). Microscopic Visualization of Metabotropic Glutamate Receptors on the Surface of Living Cells Using Bifunctional Magnetic Resonance Imaging Probes. ACS Chemical Neuroscience, 5(2), 128-137. doi:10.1021/cn400175m.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-8065-E Version Permalink: http://hdl.handle.net/21.11116/0000-0001-2C09-5
Genre: Journal Article

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http://pubs.acs.org/doi/ipdf/10.1021/cn400175m (Publisher version)
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Mishra, A, Author              
Mishra, R, Author              
Gottschalk, S1, 2, Author              
Pal, R, Author
Sim, N, Author
Engelmann, J1, 2, Author              
Goldberg, M, Author
Parker, D, Author
Affiliations:
1Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497796              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_1497794              

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 Abstract: A series of bimodal metabotropic glutamate-receptor targeted MRI contrast agents has been developed and evaluated, based on established competitive metabotropic Glu receptor subtype 5 (mGluR5) antagonists. In order to directly visualize mGluR5 binding of these agents on the surface of live astrocytes, variations in the core structure were made. A set of gadolinium conjugates containing either a cyanine dye or a fluorescein moiety was accordingly prepared, to allow visualization by optical microscopy in cellulo. In each case, surface receptor binding was compromised and cell internalization observed. Another approach, examining the location of a terbium analogue via sensitized emission, also exhibited nonspecific cell uptake in neuronal cell line models. Finally, biotin derivatives of two lead compounds were prepared, and the specificity of binding to the mGluR5 cell surface receptors was demonstrated with the aid of their fluorescently labeled avidin conjugates, using both total internal reflection fluorescence (TIRF) and confocal microscopy.

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 Dates: 2014-02
 Publication Status: Published in print
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 Identifiers: DOI: 10.1021/cn400175m
BibTex Citekey: MishraMGPSEGP2013
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Title: ACS Chemical Neuroscience
Source Genre: Journal
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Pages: - Volume / Issue: 5 (2) Sequence Number: - Start / End Page: 128 - 137 Identifier: -