Li Ya, Chase Anna R, Slivka Peter F, Baggett Clyde T, Zhao Tina X, Yin Hang
Department of Chemistry and Biochemistry, 215 UCB, University of Colorado at Boulder, Boulder, Colorado 80309-0215, USA.
Bioconjug Chem. 2008 Dec;19(12):2585-9. doi: 10.1021/bc8003815.
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.
描述了一种普遍适用的化学标记（-）-吗啡（1）的策略。合成从市售起始原料开始，两步即可完成，总产率为23%。计算机模拟和核磁共振结果表明，（-）-吗啡与其分子靶点之一Toll样受体4（TLR4）的结合不受修饰影响。分泌型胚胎碱性磷酸酶（SEAP）报告基因检测结果表明，C（3）生物素化的和未修饰的（-）-吗啡在活细胞中表现出相似的生物学活性。据我们所知，这些研究提供了首个实用且简洁的方法，用于标记各种阿片类衍生物（疼痛管理中的一类重要治疗药物），以进行生化/药理学研究。
