Design, synthesis, and evaluation of biotinylated opioid derivatives as novel probes to study opioid pharmacology.
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.
Li
Ya
Y
Department of Chemistry and Biochemistry, 215 UCB, University of Colorado at Boulder, Boulder, Colorado 80309-0215, USA.
Chase
Anna R
AR
Slivka
Peter F
PF
Baggett
Clyde T
CT
Zhao
Tina X
TX
Yin
Hang
H
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
D000701:Analgesics, Opioid; D051197:Toll-Like Receptor 4; D009020:Morphine