Photo-affinity and metabolic labeling probes based on the opioid alkaloids Journal Article
| Authors: | Duque, M. A. L.; Vallavoju, N.; Zhang, T.; Yvon, R.; Pan, Y. X.; Woo, C. M. |
| Article Title: | Photo-affinity and metabolic labeling probes based on the opioid alkaloids |
| Abstract: | 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. © 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH. |
| Keywords: | carrier protein; unclassified drug; validation process; mass spectrometry; gene expression; confocal microscopy; opiate; protein interaction; proteomics; narcotic analgesic agent; amino acid sequence; neuroblastoma; fluorescence resonance energy transfer; fluorescence microscopy; crystal structure; systemic lupus erythematosus; molecular interaction; opioids; morphine; analgesics, opioid; histone h2b; acetic acid; lysosome; photoaffinity labeling; nucleosome; acylation; alcoholism; metabolomics; hek293 cells; alkaloid; focal adhesion; matrix metalloproteinase 14; chemical proteomics; spectrin; phosphate transporter; necroptosis; humans; human; article; ec50; hek293t cell line; u2os cell line; calnexin; solute carrier protein; sh-sy5y cell line; extracellular trap; hek293s cell line; metabolic labeling; photo-affinity labeling; acetic anhydride; dialkynyl acetyl morphine |
| Journal Title: | ChemBioChem |
| Volume: | 25 |
| Issue: | 6 |
| ISSN: | 1439-4227 |
| Publisher: | Wiley V C H Verlag Gmbh |
| Date Published: | 2024-03-15 |
| Start Page: | e202300841 |
| Language: | English |
| DOI: | 10.1002/cbic.202300841 |
| PUBMED: | 38289703 |
| PROVIDER: | scopus |
| PMCID: | PMC11298156 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work