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  A new fluorogenic small molecule labeling tool for surface diffusion analysis and advanced fluorescence imaging of β-site amyloid precursor protein (APP)-cleaving enzyme 1 based on silicone rhodamine: SiR-BACE1

Karch, S., Broichhagen, J., Schneider, J., Böning, D., Hartmann, S., Schmid, B., et al. (2018). A new fluorogenic small molecule labeling tool for surface diffusion analysis and advanced fluorescence imaging of β-site amyloid precursor protein (APP)-cleaving enzyme 1 based on silicone rhodamine: SiR-BACE1. Journal of Medicinal Chemistry, 61(14), 6121-6139. doi:10.1021/acs.jmedchem.8b00387.

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JMedicinChem_61_2018_6121.pdf (beliebiger Volltext), 9MB
 
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 Urheber:
Karch, Sandra, Autor
Broichhagen, Johannes1, Autor           
Schneider, Julia, Autor
Böning, Daniel, Autor
Hartmann, Stephanie, Autor
Schmid, Benjamin, Autor
Tripal, Philipp, Autor
Palmisano, Ralf, Autor
Alzheimer, Christian, Autor
Johnsson, Kai, Autor
Huth, Tobias, Autor
Affiliations:
1Chemical Biology, Max Planck Institute for Medical Research, Max Planck Society, ou_2364732              

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 Zusammenfassung: β-site APP-cleaving enzyme 1 (BACE1) is a major player in the pathogenesis of Alzheimer’s disease. Structural and functional fluorescence microscopy offers a powerful approach to learn about the physiology and pathophysiology of this protease. Up to now, however, common labeling techniques either require genetic manipulation, use large antibodies, or are not compatible with live cell imaging. Fluorescent small molecules that specifically bind to the protein of interest can overcome these limitations. Herein, we introduce SiR-BACE1, a conjugate of the BACE1 inhibitor S-39 and SiR647, as a novel fluorogenic, tag-free, and antibody-free label for BACE1. We present its chemical development, characterize its photo-physical and pharmacologic properties, and evaluate its behavior in solution, in over-expression systems, and in native brain tissue. We demonstrate its applicability in confocal, stimulated emission depletion (STED), and dynamic single molecule microscopy. First functional studies with SiR-BACE1 on the surface mobility of BACE1 revealed a markedly confined diffusion pattern.

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Sprache(n): eng - English
 Datum: 2018-04-042018-06-252018-07-01
 Publikationsstatus: Erschienen
 Seiten: 19
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Titel: Journal of Medicinal Chemistry
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: Washington DC : ACS Publications
Seiten: - Band / Heft: 61 (14) Artikelnummer: - Start- / Endseite: 6121 - 6139 Identifikator: ISSN: 0022-2623
CoNE: https://pure.mpg.de/cone/journals/resource/110992357271168