Synthesis and Evaluation of Biotinylated Small Molecular Drugs with Long Chain / 中国药学杂志

ABSTRACT

OBJECTIVE: To set up an easy and effective method for biotinylation of small molecule drugs with long chain. METHODS: Biotinylated 6-aminocaproic acid was synthesized as intermediate by one step method, doxorubicin(DOX) with auto-fluorescence was used as the first drug, and by DCC and DMAP catalysis, biotinylated DOX was synthesized. Using the double fluorescence system of DOX, the binding ability of biotinylated DOX to avidin and its biological activity were determined. When verified to be reasonable and effective, the method was applied to catalyze biotinylated paclitexal (PTX) which didn′t have auto-fluorescence itself, and the physical and chemical characteristics, and biological activities as well as the visualization were tested. RESULTS: The binding rate of synthesized DOX to avidin was 93.7%; the cells inhibition rate and localization were the same as DOX; the purity of biotinylated PTX was 84.42%, and the structure shown by NMR was correct; the cell inhibition rate was the same as PTX; the combination of PTX with microtubules was observed by visual modification. CONCLUSION: The method supplies a temperate way for biotinylation, and can be used for the synthesis and visualization of small molecules as probes and research of drug mechanism.