Photo-affinity and Metabolic Labeling Probes Based on the Opioid Alkaloids.
Mark Anthony Leon DuqueNandini VallavojuTiffany ZhangRobert YvonYing-Xian PanChristina M WooPublished in: Chembiochem : a European journal of chemical biology (2024)
The opioids are powerful analgesics yet possess contingencies that can lead to opioid-use disorder. Chemical probes derived from the opioid alkaloids can provide deeper insight into the molecular interactions in a cellular context. Here, we designed and developed photo-click morphine (PCM-2) as a photo-affinity probe based on morphine and dialkynyl-acetyl morphine (DAAM) as a metabolic acetate reporter based on heroin. Application of these probes to SH-SY5Y, HEK293T, and U2OS cells revealed that PCM-2 and DAAM primarily localize to the lysosome amongst other locations inside the cell by confocal microscopy and chemical proteomics. Interaction site identification by mass spectrometry revealed the mitochondrial phosphate carrier protein, solute carrier family 25 member 3, SLC25A3, and histone H2B as acylation targets of DAAM. These data illustrate the utility of chemical probes to measure localization and protein interactions in a cellular context and will inform the design of probes based on the opioids in the future.
Keyphrases
- living cells
- small molecule
- chronic pain
- pain management
- single molecule
- fluorescent probe
- fluorescence imaging
- mass spectrometry
- single cell
- protein protein
- nucleic acid
- induced apoptosis
- oxidative stress
- cell therapy
- photodynamic therapy
- crispr cas
- electronic health record
- electron transfer
- stem cells
- high performance liquid chromatography
- cell proliferation
- current status
- mesenchymal stem cells
- endoplasmic reticulum stress
- artificial intelligence
- signaling pathway
- gas chromatography