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

Karch S, Broichhagen J, Schneider J, Boening D, Hartmann S, Schmid B, Tripal P, Palmisano R, Alzheimer C, Johnsson K, Huth T (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Journal of Medicinal Chemistry American Chemical Society

Book Volume: 61

Pages Range: 6121-6139

Journal Issue: 14

DOI: 10.1021/acs.jmedchem.8b00387

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.

Authors with CRIS profile

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

Involved external institutions

Max-Planck-Institut für medizinische Forschung / Max Planck Institute for Medical Research DE Germany (DE) Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light DE Germany (DE)

How to cite

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.

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