A New Fluorogenic Small-Molecule Labeling Tool for Surface Diffusion Analysis and Advanced Fluorescence Imaging of β-Site Amyloid Precursor Protein-Cleaving Enzyme 1 Based on Silicone Rhodamine: SiR-BACE1

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Karch S, Broichhagen J, Schneider J, Boening D, Hartmann S, Schmid B, Tripal P, Palmisano R, Alzheimer C, Johnsson K, Huth T
Zeitschrift: Journal of Medicinal Chemistry
Jahr der Veröffentlichung: 2018
Band: 61
Heftnummer: 14
Seitenbereich: 6121-6139
ISSN: 0022-2623


Abstract

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 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 photophysical and pharmacologic properties, and evaluate its behavior in solution, in overexpression systems, and in native brain tissue. We demonstrate its applicability in confocal, stimulated emission depletion and dynamic single-molecule microscopy. The first functional studies with SiR-BACE1 on the surface mobility of BACE1 revealed a markedly confined diffusion pattern.


FAU-Autoren / FAU-Herausgeber

Alzheimer, Christian Prof. Dr.
Lehrstuhl für Physiologie
Hartmann, Stephanie
Lehrstuhl für Physiologie
Huth, Tobias PD Dr. Dr.
Lehrstuhl für Physiologie
Karch, Sandra
Lehrstuhl für Physiologie
Palmisano, Ralf Dr.
Optical Imaging Center Erlangen (OICE)
Schmid, Benjamin Dr.
Optical Imaging Center Erlangen (OICE)
Schneider, Julia
Lehrstuhl für Biochemie und Molekulare Medizin
Tripal, Philipp Dr.
Optical Imaging Center Erlangen (OICE)


Autor(en) der externen Einrichtung(en)
Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light
Max-Planck-Institut für medizinische Forschung / Max Planck Institute for Medical Research


Zitierweisen

APA:
Karch, S., Broichhagen, J., Schneider, J., Boening, D., Hartmann, S., Schmid, B.,... Huth, T. (2018). A New Fluorogenic Small-Molecule Labeling Tool for Surface Diffusion Analysis and Advanced Fluorescence Imaging of β-Site Amyloid Precursor Protein-Cleaving Enzyme 1 Based on Silicone Rhodamine: SiR-BACE1. Journal of Medicinal Chemistry, 61(14), 6121-6139. https://dx.doi.org/10.1021/acs.jmedchem.8b00387

MLA:
Karch, Sandra, et al. "A New Fluorogenic Small-Molecule Labeling Tool for Surface Diffusion Analysis and Advanced Fluorescence Imaging of β-Site Amyloid Precursor Protein-Cleaving Enzyme 1 Based on Silicone Rhodamine: SiR-BACE1." Journal of Medicinal Chemistry 61.14 (2018): 6121-6139.

BibTeX: 

Zuletzt aktualisiert 2019-25-02 um 10:10