雷公藤，或林雷龚滕Triptolide的动画片
本帖最后由 namlow 于 2011-7-11 21:15 编辑解决一个中国传统医学的奥秘：分子机制的发现揭示了抗肿瘤的可能性[复制链接]
雷公藤，或林雷龚滕Triptolide
http://www.nature.com/nchembio/journal/v7/n3/images/nchembio.522-comp1.gif
的3D分子结构1:
http://www.nature.com/nchembio/journal/v7/n3/compound/nchembio.522_comp1_3d.html
Compound 1
的动画片:
http://player.youku.com/player.php/sid/XMjg0MTc4MTA4/v.swf
有中文稿了:
http://www.bioon.com/biology/cancer/479610.shtml
Nat Chem Biol.:雷公藤中分离出一种天然物质 或可用于抗癌药开发 2011-4-1 14:09:36 1104 来源：科技日报 作者：生物谷 【大 中 小】
http://www.bioon.com/images/but.png
雷公藤是一种传统中药，数百年来用于治疗风湿类关节炎等多种疾病。据美国物理学家组织网近日报道，美国约翰·霍普金斯医学院从雷公藤中分离出一种天然物质，具有抑制细胞中基因控制体系的功能，以此为基础有望开发出新型的抗癌药物。该研究作为封面文章发表在3月份出版的《自然·化学生物学》上。http://www.bioon.com/biology/UploadFiles/201104/2011040114130347.jpg
“这种中药的提取物可用于治疗病人的整体症状，在抵抗炎症、免疫制疫、避孕以及提高抗癌性等方面具有极高评价。”约翰·霍普金斯大学药理学与分子科学教授刘俊欧（音译）说，“早在1972年，我们就已知道一种名为雷公藤内酯的活性物质，能使细胞生长中断，直到现在才找到原因。”
刘俊欧解释说，雷公藤内酯是从中药雷公藤中提取的活性成分，在动物实验中能有效对抗癌症、关节炎和皮肤移植排斥。而且低剂量条件下，显示出具有抑制国家癌症研究中心所列出的全部60种细胞系的能力，甚至能杀死某些癌细胞系。
研究小组系统地实验了雷公藤内酯对多种基因控制蛋白的作用，对细胞中合成的新DNA、RNA和蛋白质进行了观察。他们用雷公藤内酯处理海拉癌细胞，经1个小时后和没经过处理的癌细胞对比，发现经过雷公藤内酯处理的癌细胞合成新的蛋白质和DNA所花的时间更长，而RNA的再生几乎立刻就被抑制了。进一步观察制造RNA的3组酶，发现低剂量雷公藤内酯只能抑制其中1种，即RNAPII。
由于RNAPII酶需要几种更小的蛋白质辅助，研究人员在试管中将一小片基因和RNAPII组分混合，在一些试管中加入雷公藤内酯而另一些不加，观察发现，含有名为TFIIH聚簇的蛋白酶组合，在加入雷公藤内酯的条件下都会停止作用。进一步，TFIIH由10个单独蛋白质构成，其中多个具有明显可测的活性。根据已知信息和实验，雷公藤内酯能和其中之一XPB蛋白直接结合而抑制酶的活性。
刘俊欧说：“其他研究人员已经发现雷公藤内酯能和一种未知的蛋白质结合，却尚未识别出是什么蛋白质，而我们相当确定这正是XPB蛋白质。”
为了证实是雷公藤内酯和XPB之间的互相作用停止了细胞生长，他们还制造了12种含有雷公藤内酯的不同活性化学药物，用这12种药物以不同的剂量来处理海拉癌细胞。通过计算细胞数量、测试XPB活性水平，研究小组发现这二者是相关的：XPB活性越低，细胞停止生长效果越明显，显示出药效越好，反之亦然。（生物谷Bioon.com）
生物谷推荐原文出处：
Nature Chemical Biology, 2011; 7 (3): 182 DOI: 10.1038/nchembio.522
XPB, a subunit of TFIIH, is a target of the natural product triptolideDenis V Titov, Benjamin Gilman, Qing-Li He, Shridhar Bhat, Woon-Kai Low, Yongjun Dang, Michael Smeaton, Arnold L Demain, Paul S Miller, Jennifer F Kugel, James A Goodrich, Jun O Liu
Triptolide (1) is a structurally unique diterpene triepoxide isolated from a traditional Chinese medicinal plant with anti-inflammatory, immunosuppressive, contraceptive and antitumor activities. Its molecular mechanism of action, however, has remained largely elusive to date. We report that triptolide covalently binds to human XPB (also known as ERCC3), a subunit of the transcription factor TFIIH, and inhibits its DNA-dependent ATPase activity, which leads to the inhibition of RNA polymerase II–mediated transcription and likely nucleotide excision repair. The identification of XPB as the target of triptolide accounts for the majority of the known biological activities of triptolide. These findings also suggest that triptolide can serve as a new molecular probe for studying transcription and, potentially, as a new type of anticancer agent through inhibition of the ATPase activity of XPB.
本帖最后由 namlow 于 2011-7-13 15:45 编辑
为了证实是雷公藤内酯和XPB之间的互相作用停止了细胞生长，他们还制造了12种含有雷公藤内酯的不同活性化学药物，用这12种药物以不同的剂量来处理海拉癌细胞。
12种含有雷公藤内酯的不同活性化学药物的动画{其中1,2,3,4中的1是JAVA的3D动画}在:
Compound data index From XPB, a subunit of TFIIH, is a target of the natural product triptolide
[*] Denis V Titov
[*] Benjamin Gilman
[*] Qing-Li He
[*] Shridhar Bhat
[*] Woon-Kai Low
[*] Yongjun Dang
[*] Michael Smeaton
[*] Arnold L Demain
[*] Paul S Miller
[*] Jennifer F Kugel
[*] James A Goodrich
[*] Jun O Liu
Nature Chemical Biology 7,182–188(2011)doi:10.1038/nchembio.522 Supplementary Information
CompoundsDownload all compounds in a single file (36 KB)back to article
[*] http://www.nature.com/nchembio/journal/v7/n3/thumbs/nchembio.522-comp1.gif Compound 1 Triptolide View in PubChem
[*]View in 3D (7 KB)
[*]Download ChemDraw file of structure (3 KB)
[*]Download CML file (4 KB)
[*]Download Molfile (3 KB)
[*] http://www.nature.com/nchembio/journal/v7/n3/thumbs/nchembio.522-comp2.gif Compound 2 14-epi-Triptolide View in PubChem
[*]View in 3D (7 KB)
[*]Download ChemDraw file of structure (3 KB)
[*]Download CML file (4 KB)
[*]Download Molfile (3 KB)
[*] http://www.nature.com/nchembio/journal/v7/n3/thumbs/nchembio.522-comp3.gif Compound 3 5α-Hydroxytriptolide View in PubChem
[*]View in 3D (7 KB)
[*]Download ChemDraw file of structure (3 KB)
[*]Download CML file (4 KB)
[*]Download Molfile (3 KB)
[*] http://www.nature.com/nchembio/journal/v7/n3/thumbs/nchembio.522-comp4.gif Compound 4 Triptonide View in PubChem
[*]View in 3D (7 KB)
[*]Download ChemDraw file of structure (3 KB)
[*]Download CML file (4 KB)
[*]Download Molfile (3 KB)
[*] http://www.nature.com/nchembio/journal/v7/n3/thumbs/nchembio.522-comp5.gif Compound 5 5α-Hydroxytriptonide View in PubChem
[*]View in 3D (6 KB)
[*]Download ChemDraw file of structure (3 KB)
[*]Download CML file (4 KB)
[*]Download Molfile (3 KB)
[*] http://www.nature.com/nchembio/journal/v7/n3/thumbs/nchembio.522-comp7.gif Compound 7 14-(1H-Imidazole-1-carbothioyl)triptolide View in PubChem
[*]View in 3D (8 KB)
[*]Download ChemDraw file of structure (4 KB)
[*]Download CML file (5 KB)
[*]Download Molfile (3 KB)
[*] http://www.nature.com/nchembio/journal/v7/n3/thumbs/nchembio.522-comp8.gif Compound 8 14-Deoxy-14α-fluorotriptolide View in PubChem
[*]View in 3D (6 KB)
[*]Download ChemDraw file of structure (3 KB)
[*]Download CML file (4 KB)
[*]Download Molfile (3 KB)
[*] http://www.nature.com/nchembio/journal/v7/n3/thumbs/nchembio.522-comp9.gif Compound 9 (14S)-Triptolide-14-spiro-1'-oxirane View in PubChem
[*]View in 3D (7 KB)
[*]Download ChemDraw file of structure (3 KB)
[*]Download CML file (4 KB)
[*]Download Molfile (3 KB)
[*] http://www.nature.com/nchembio/journal/v7/n3/thumbs/nchembio.522-comp10.gif Compound 10 (14S)-5α-Hydroxytriptolide-14-spiro-1'-oxirane View in PubChem
[*]View in 3D (7 KB)
[*]Download ChemDraw file of structure (3 KB)
[*]Download CML file (4 KB)
[*]Download Molfile (3 KB)
[*] http://www.nature.com/nchembio/journal/v7/n3/thumbs/nchembio.522-comp11.gif Compound 11 (14S)-12-Deoxy-12β-chloro-13α-hydroxytriptolide-14-spiro-1'-oxirane View in PubChem
[*]View in 3D (7 KB)
[*]Download ChemDraw file of structure (4 KB)
[*]Download CML file (4 KB)
[*]Download Molfile (3 KB)
[*] http://www.nature.com/nchembio/journal/v7/n3/thumbs/nchembio.522-comp12.gif Compound 12 7-Deoxy-8β-hydroxytriptolide View in PubChem
[*]View in 3D (7 KB)
[*]Download ChemDraw file of structure (3 KB)
[*]Download CML file (4 KB)
[*]Download Molfile (3 KB)
页:
[1]