American Chemical Society
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Design, Synthesis, and Evaluation of Biotinylated Opioid Derivatives as Novel Probes to Study Opioid Pharmacology

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journal contribution
posted on 2008-12-17, 00:00 authored by Ya Li, Anna R. Chase, Peter F. Slivka, Clyde T. Baggett, Tina X. Zhao, Hang Yin
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 C3 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.