热休克蛋白90(Hsp90)抑制剂荧光标记探针化合物的设计合成  

Design and synthesis of fluorescence polarization probes for Hsp90

作　　者：李永强[1] 袁霞[1] 周玉美[1] 罗志刚[1] 陈晓光[1] 俞晓明[1] 

机构地区：[1]中国医学科学院北京协和医学院药物研究所,北京100050

出　　处：《中国药物化学杂志》2009年第3期170-173,180,共5页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(30772634)

摘　　要：目的寻找新型Hsp90抑制剂荧光标记探针化合物,用于建立高通量荧光偏振筛选模型。方法选择高活性的小分子Hsp90抑制剂(化合物1),以氟硼二吡咯为荧光标记物质,对小分子化合物进行标记,并进行荧光偏振测试窗口测定,确定正确的标记位置。结果与结论设计合成了两个未见文献报道的全新探针化合物,化合物结构经IR、1H-NMR、MS和HR-MS谱确证。初步测试结果表明,当Hsp90的浓度为50nmol.L-1时,探针Ⅱ的测试窗口达到了96mp,能初步满足筛选方法建立的要求,为进一步的优化筛选打下了一定的基础。Aim To design and synthesize of more stable and less expensive novel fluorescence labelled probes for Hsp90 inhibitor for high throughput assay. Methods A small molecule inhibitor （compound 1 ） with high activity was selected to be labelled by BODIPY. The designed probes were synthesized and fluorescence polarized assay window were also determined. Results and conclusion Two fluorescence probes for Hsp90 inhibitors high throughput assay were designed and synthesized, and their structures were confirmed by IR, ^1H-NMR, MS and HR-MS. The preliminary data showed that, at the concentration 50 nmol·L^-1 of Hsp90, the measured polarization assay window provided by probe-Ⅱ is up to 96 mp,indicating that this probe might not only be practically useful in assay development, but also provide evidence for further optimization.

关 键 词：HSP90抑制剂 荧光标记探针 荧光偏振 高通量筛选 

分 类 号：R914[医药卫生—药物化学]