期刊文献+

热休克蛋白90(Hsp90)抑制剂荧光标记探针化合物的设计合成 被引量:1

Design and synthesis of fluorescence polarization probes for Hsp90
收藏 分享 导出
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.
作者 李永强 袁霞 周玉美 罗志刚 陈晓光 俞晓明 LI Yong-qiang, YUAN Xia,ZHOU Yu-mei ,LUO Zhi-gang ,CHEN Xiao-guang, YU Xiao-ming ( Institute of Materia Mediea, Chinese Academy of Medical Sciences & Peking Union Medical College ,Beijing lO0050 , China )
出处 《中国药物化学杂志》 CAS CSCD 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)
关键词 HSP90抑制剂 荧光标记探针 荧光偏振 高通量筛选 Hsp90 inhibitors fluorescence labelled probes fluorescence polarize high throughput assay
作者简介 李永强(1979-),男(汉族),河北保定人,实习研究员,主要从事药物化学研究工作; 俞晓明(1968-),男(汉族),浙江桐庐人,硕士生导师,主要从事药物化学研究工作,Tel:(010)63165259,E-mail:mingxyu@imm.ac.cn。
  • 相关文献

参考文献10

  • 1ZHANG H, BURROWS F. Targeting multiple signal transduction pathways through inhibition of Hsp90 [ J ]. J Mol Med,2004,82 ( 8 ) :488 - 499. 被引量:1
  • 2ISAACS J S, XU W P, NECKERS L. Heat shock protein 90 as a molecular target for cancer therapeutics[ J]. Cancer Cell ,2003,3 (3) :213 - 217. 被引量:1
  • 3MOULICK K,CLEMENT C C,AGUIRRE J,et al. Synthesis of a red-shifted fluorescence polarization probe for Hsp90[ J]. Bioorg Med Chem Lett,2006, 16(17) :4515 -4518. 被引量:1
  • 4DYMOCK B W, BARRIL X, BROUGH P A, et al. Novel, potent small-molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design [ J ]. J Med Chem, 2005,48 ( 13 ) : 4212 -4215. 被引量:1
  • 5KIM J, FELTS S, LLAGUER L, et al. Development of a fluorescence polarization assay for themolecular chaperone Hsp90 [ J ]. J Biomol Screen,2004,9 (5) : 375 - 381. 被引量:1
  • 6BARRIL X,BESWICK M C,COLLIER A,et al. 4- Amino derivatives of the Hspg0 inhibitor CCT018159[ J]. Bioorg Med Chem Lett, 2006, 16 (9) :2543 -2548. 被引量:1
  • 7BROWN F J,BERNSTEIN P R,CRONK L A,et al. Hydroxyacetophenone-derived antagonists of the peptidoleukotrienes [J]. J Med Chem, 1989,32 (4) : 807 - 826. 被引量:1
  • 8TAHTAOUI C, GUILLIER F, KLOTZ P, et al. Fluorescent pirenzepine derivatives as potential bitopic ligands of the human M1 muscarinic receptor[ J ]. J Med Chem ,2005,48 (24) :7847 - 7859. 被引量:1
  • 9MALAN S F, van MARLE A, MENGE W M, et al. Fluorescent ligands for the histamine H2 receptor: synthesis and preliminary characterization [ J ]. Bioorg Med Chem,2004,12 ( 24 ) : 6495 - 6503. 被引量:1
  • 10YOON N M, PAK C S, BROWN H C, et al. Selective reductions. XIX. Rapid reaction of carboxylic acids with borane-tetrahydrofuran. Remarkably con- venient procedure for the selective conversion of carboxylic acids to the corresponding alcohols in the presence of other functional groups [J]. J Org Chem, 1973,38 ( 16 ) : 2786 - 2789. 被引量:1

同被引文献4

引证文献1

二级引证文献1

投稿分析

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部 意见反馈