...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Semisynthetic Derivatives of Concanamycin A and C, as Inhibitors of V-and P-Type ATPases: Structure-Activity Investigations and Developments of Photoaffinity Probes
【24h】

Semisynthetic Derivatives of Concanamycin A and C, as Inhibitors of V-and P-Type ATPases: Structure-Activity Investigations and Developments of Photoaffinity Probes

机译：伴刀豆球蛋白A和C，作为V型和P型ATPase抑制剂的半合成衍生物：结构亲和性研究和光亲和性探针的发展。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

V-type A TPases are inhibited by the plecomacrolides bafilomycin and concanamycin, which exert their inhibitory potential at nanomolar concentrations. In addition, some P-type A TPases are inhibited at micromolar concentrations. We initiated intensive structure-activity investigations with semisynthetic concanamycin derivatives to approach the following two questions: (i) What is the pharmacophor, the structural key element, of the plecomacrolides that leads to their inhibitory potential against V- and P-type ATPases? (ii) Where is the binding site within these two different types of ATPases? In a first step, we examined where chemical modifications (O-acylations, substitutions, eliminations) could be placed without seriously affecting the inhibitory potential of the macrolides. In a second step, we used the knowledge of these structure-activity investigations to introduce traceable elements (fluorescent or radioactive) or nitrene- generating azido or carbene-generating diazirine-groups able to bind the inhibitors to their target covalently. These studies led finally to the synthesis of two photoaffinity probes that were used in labeling experiments with the purified plasma membrane V-type ATPase of Manduca sexta (described i!1 a following paper, Huss, M., Gassel, M., .Ingenhorst, G., Drose, S., Zeeck, A., Altendorf, K., Wieczorek, H., manuscript submitted).
机译：V型A TP酶被plecomacrolides bafilomycin和conconamycin抑制，它们在纳摩尔浓度下发挥抑制作用。另外，在微摩尔浓度下，某些P型A TP酶被抑制。我们针对半合成伴刀豆球菌衍生物开展了深入的结构活性研究，以解决以下两个问题：（i）plecoacrolides的药效学是结构关键要素是什么，它们可导致其对V型和P型ATP酶的抑制潜力？ （ii）这两种不同类型的ATPase中的结合位点在哪里？在第一步中，我们研究了在不严重影响大环内酯类药物抑制潜力的情况下可以进行化学修饰（O-酰化，取代，消除）的地方。在第二步中，我们利用了这些结构活性研究的知识，引入了可追踪的元素（荧光或放射性）或生成亚硝基的叠氮基或生成卡宾的二叠氮基，它们能够将抑制剂共价结合至其靶标。这些研究最终导致了两种光亲和探针的合成，该探针用于曼杜卡六倍体纯化的质膜V型ATPase的标记实验中（在下文中由Huss，M.，Gassel，M.，.Ingenhorst描述，G.，Drose，S.，Zeeck，A.，Altendorf，K.，Wieczorek，H。，提交的手稿）。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号