公开(公告)号：US07785900B1

公开(公告)日：2010-08-31

申请号：US11652432

申请日：2007-01-11

申请人： Peter C. Simons ,  Larry A. Sklar ,  Eric R. Prossnitz ,  Angela Wandinger-Ness ,  Mathewos Z. Tessema ,  John C. Reed ,  Dayong Zhai

发明人： Peter C. Simons ,  Larry A. Sklar ,  Eric R. Prossnitz ,  Angela Wandinger-Ness ,  Mathewos Z. Tessema ,  John C. Reed ,  Dayong Zhai

IPC分类号： G01N33/543 ,  G01N33/53

CPC分类号： G01N33/54393 ,  G01N33/543

摘要： The present invention relates generally to glutathione derivatized beads which are adapted for use in conjunction with glutathione-S-transferase fusion proteins (generally, GST fusion proteins, which contain a fluorescent label such as fluorescent green protein) for use in flow cytometry. The present invention also relates to methods for detecting and/or quantifying interactions between a GST fusion protein and their binding partners, in particular, labeled binding partners such as fluorescently labeled binding partners. By creating glutathione beads with an appropriate high or increased site density, disadvantages often associated with low affinity systems and quick off-rates in solution may be resolved to provide a workable system and method. Methods of identifying potential agonists, antagonists and regulator compounds of proteins fused to GST from libraries of compounds represents another aspect of the present invention.

摘要翻译： 本发明一般涉及适用于与流式细胞术中使用的谷胱甘肽-S-转移酶融合蛋白（通常为含有荧光标记如荧光绿蛋白的GST融合蛋白）结合使用的谷胱甘肽衍生化珠粒。 本发明还涉及用于检测和/或定量GST融合蛋白与其结合配偶体，特别是标记的结合配偶体如荧光标记的结合配偶体之间的相互作用的方法。 通过产生具有适当的高或增加的位点密度的谷胱甘肽珠，可以解决通常与低亲和力系统相关的缺点和解决方案中的快速关闭速率，以提供可行的系统和方法。 从化合物文库鉴定与GST融合的蛋白质的潜在激动剂，拮抗剂和调节剂化合物的方法代表本发明的另一方面。

公开(公告)号：US20090163577A1

公开(公告)日：2009-06-25

申请号：US12325315

申请日：2008-12-01

申请人： John C. Reed ,  Dayong Zhai

发明人： John C. Reed ,  Dayong Zhai

IPC分类号： A61K31/35 ,  C12Q1/18 ,  G01N33/574 ,  C07D493/02 ,  A61P35/00

CPC分类号： A61K31/35 ,  G01N33/57484 ,  G01N2500/02 ,  G01N2500/10

摘要： The cytotoxic natural product gambogic acid (GA) competes for BH3 peptide binding sites on several anti-apoptotic members of the Bcl-2 family of proteins and neutralizes the ability of these proteins to suppress release of apoptogenic proteins from isolated mitochondria. Structure-function analysis of GA using analogs suggested a general correlation between BH3 competition and cytoxicity activity. Compositions and methods are provided for using GA and its derivatives for treating cancer and for discovering other compounds that are useful for treating cancer through their interaction with Bcl-2-family proteins.

摘要翻译： 细胞毒性天然产物葡萄糖酸（GA）与Bcl-2蛋白家族的几种抗凋亡成员竞争BH3肽结合位点，并中和这些蛋白质抑制细胞凋亡蛋白从分离的线粒体释放的能力。 使用类似物的GA的结构功能分析表明BH3竞争与细胞毒性活性之间的一般相关性。 提供了使用GA及其衍生物治疗癌症并发现其它可用于通过与Bcl-2家族蛋白质相互作用治疗癌症的化合物的组合物和方法。

公开(公告)号：US20090069324A1

公开(公告)日：2009-03-12

申请号：US12130735

申请日：2008-05-30

申请人： John C. Reed ,  Dayong Zhai ,  Shinichi Kitada ,  Eduard Sergienko

发明人： John C. Reed ,  Dayong Zhai ,  Shinichi Kitada ,  Eduard Sergienko

IPC分类号： A61K31/496 ,  A61K31/5377 ,  G01N33/53 ,  A61P35/00

CPC分类号： A61K31/496 ,  A61K31/5377 ,  G01N2500/02

摘要： Compounds that bind to Bfl-1 as well as conjugates of such compounds are provided. Various embodiments additionally provide methods of using such compounds to identify additional anti-apoptotic Bfl-1 binding compounds. Methods of using such compounds to increase apoptosis in a cell are also provided.

摘要翻译： 提供了结合Bfl-1的化合物以及这些化合物的缀合物。 各种实施方案另外提供了使用这些化合物鉴定另外的抗凋亡Bfl-1结合化合物的方法。 还提供了使用这些化合物增加细胞凋亡的方法。