Abstract
CCG-1423 and related analogues represent a new class of inhibitors of Rho/MKL1/SRF-mediated gene transcription, a pathway that has been implicated in both cancer and fibrosis. The molecular target for these compounds is unknown. To facilitate its identification, a series of tag-free photoaffinity probes was designed and synthesized, each one containing a photoactivatable group and an acetylenic end group for subsequent attachment to a fluorescent tag using click chemistry. All were confirmed to maintain biological activity in a cell-based assay for inhibition of SRE-Luc expression. The functional activity of the most potent probe 24 was further confirmed in an assay for PC-3 cell migration. Photolysis of 24 in intact PC-3 cells followed by cell lysis, click ligation of a fluorescent dye, and gel electrophoresis revealed specific labeling of a single 24 kDa band that could be blocked with an active competitor. Future work will focus on identifying the labeled protein(s).
Original language | English (US) |
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Pages (from-to) | 966-973 |
Number of pages | 8 |
Journal | Beilstein Journal of Organic Chemistry |
Volume | 9 |
DOIs | |
State | Published - May 21 2013 |
Keywords
- CCG-1423
- Click ligation
- Photoaffinity labeling
- Rho pathway inhibitor
- Tag-free photoprobe
- Target identification
ASJC Scopus subject areas
- Organic Chemistry