酶法合成埃坡霉素 A 糖苷。
Enzymatic synthesis of epothilone A glycosides.
机构信息
Institute of Biomolecule Reconstruction (iBR), Department of Pharmaceutical Engineering, SunMoon University, Chungnam 336-708, Asan-si, Republic of Korea.
Department of Chemistry and Nano Science, Ewha Womans University, Seoul 120-750, Republic of Korea.
出版信息
AMB Express. 2014 Mar 20;4:31. doi: 10.1186/s13568-014-0031-1. eCollection 2014.
Epothilones are extremely cytotoxic chemotherapeutic agents with epoxide, thiazole, and ketone groups that share equipotent kinetic similarity with taxol. The in vitro glycosylation catalyzed by uridine diphosphate glucosyltransferase (YjiC) from Bacillus licheniformis generated six novel epothilone A glycoside analouges including epothilone A 7-O-β-D-glucoside, epothilone A 7-O-β-D-galactoside, epothilone A 3,7-O-β-D-digalactoside, epothilone A 7-O-β-D-2-deoxyglucoside, epothilone A 7-O-β-L-rhamnoside, and epothilone A 7-O-β-L-fucoside. Epothilone A 7-O-β-D-glucoside was structurally elucidated by ultra-high performance liquid chromatography-photo diode array (UPLC-PDA) conjugated with high resolution quantitative time-of-flight-electrospray ionization mass spectroscopy (HR-QTOF ESI-MS/MS) supported by one-and two-dimensional nuclear magnetic resonance studies whereas other epothilone A glycosides were characterized by UPLC-PDA and HR-QTOF ESI-MS/MS analyses. The time dependent conversion study of epothilone A to epothilone A 7-O-β-D-glucoside found to be maximum (~26%) between 3 h to 5 h incubation.
埃坡霉素是具有环氧、噻唑和酮基的极其细胞毒性化疗药物，与紫杉醇具有等效的动力学相似性。来自地衣芽孢杆菌的尿苷二磷酸葡萄糖基转移酶 (YjiC) 催化的体外糖基化生成了六种新型埃坡霉素 A 糖苷类似物，包括埃坡霉素 A 7-O-β-D-葡萄糖苷、埃坡霉素 A 7-O-β-D-半乳糖苷、埃坡霉素 A 3,7-O-β-D-二半乳糖苷、埃坡霉素 A 7-O-β-D-2-脱氧葡萄糖苷、埃坡霉素 A 7-O-β-L-鼠李糖苷和埃坡霉素 A 7-O-β-L-岩藻糖苷。埃坡霉素 A 7-O-β-D-葡萄糖苷的结构通过超高效液相色谱-光电二极管阵列 (UPLC-PDA) 与高分辨率定量飞行时间-电喷雾电离质谱 (HR-QTOF ESI-MS/MS) 结合进行结构解析，二维核磁共振研究支持；而其他埃坡霉素 A 糖苷则通过 UPLC-PDA 和 HR-QTOF ESI-MS/MS 分析进行表征。埃坡霉素 A 向埃坡霉素 A 7-O-β-D-葡萄糖苷的时间依赖性转化研究发现，在 3 小时至 5 小时孵育期间转化率最高（约 26%）。
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