title: Design, synthesis, and evaluation of biotinylated opioid derivatives as novel probes to study opioid pharmacology.
abstract: A generally applicable strategy of chemically labeling (-)-morphine (1) is described. The synthesis starts from commercially available starting materials and can be completed in two steps with an overall yield of 23%. In silico simulation and NMR results show that the binding of (-)-morphine to one of its molecular targets, toll-like receptor 4 (TLR4), was not affected by the modification. Secreted embryonic alkaline phosphatase (SEAP) reporter assay results demonstrate that C(3) biotinylated and unmodified (-)-morphine show similar biological activities in live cells. To our knowledge, these studies provide the first practical and concise method to label various opioid derivatives, a group of important therapeutics in pain management, for biochemical/pharmacological studies.
authors.affiliation: Department of Chemistry and Biochemistry, 215 UCB, University of Colorado at Boulder, Boulder, Colorado 80309-0215, USA.
authors.forename: Ya
authors.initials: Y
authors.lastname: Li
authors.forename: Anna R
authors.initials: AR
authors.lastname: Chase
authors.forename: Peter F
authors.initials: PF
authors.lastname: Slivka
authors.forename: Clyde T
authors.initials: CT
authors.lastname: Baggett
authors.forename: Tina X
authors.initials: TX
authors.lastname: Zhao
authors.forename: Hang
authors.initials: H
authors.lastname: Yin
mesh_terms: D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D019921:Biotinylation; D002417:Cattle; D002460:Cell Line; D019295:Computational Biology; D015195:Drug Design; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D009020:Morphine / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D051197:Toll-Like Receptor 4; D009020:Morphine