Abstract
While the constitutive, 26S proteasome plays an important role in regulating many important cellular processes, a variant form known as the immunoproteasome is thought to primarily function in adaptive immune responses. However, recent studies indicate an association of immunoproteasomes with many physiological disorders such as cancer, neurodegenerative, and inflammatory diseases. Despite this, the detailed functions of the immunoproteasome remain poorly understood. Immunoproteasome-specific probes are essential to gain insight into immunoproteasome function. Here, we describe for the first time the development of cell-permeable activity-based fluorescent probes, UK101-Fluor and UK101-B660, which selectively target the catalytically active LMP2/β1i subunit of the immunoproteasome. These probes facilitate rapid detection of the cellular localization of catalytically active immunoproteasomes in living cells, providing a valuable tool to analyze immunoproteasome functions. Additionally, as LMP2/β1i may serve as a potential tumor biomarker, an LMP2/β1i-targeting fluorescent imaging probe may be applicable to a rapid readout assay to determine tumor LMP2/β1i levels.
Original language | English |
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Pages (from-to) | 607-613 |
Number of pages | 7 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 20 |
Issue number | 2 |
DOIs | |
State | Published - Jan 15 2012 |
Bibliographical note
Funding Information:This work has been supported by the Markey Cancer Foundation and NIH ( CA131059 ). We thank members of the Kim lab for their helpful comments on the manuscript.
Keywords
- Fluorescent probes
- Immunoproteasome
- LMP2
- Near-infrared fluorescent probe
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry