...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Medicinal Chemistry >Anilinoquinazoline inhibitors of fructose 1,6-bisphosphatase bind at a novel allosteric site: synthesis, in vitro characterization, and X-ray crystallography.
【24h】

Anilinoquinazoline inhibitors of fructose 1,6-bisphosphatase bind at a novel allosteric site: synthesis, in vitro characterization, and X-ray crystallography.

机译：果糖1,6-双磷酸酶的苯胺喹唑啉抑制剂在新的变构位点结合：合成，体外表征和X射线晶体学。

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

The synthesis and in vitro structure-activity relationships (SAR) of a novel series of anilinoquinazolines as allosteric inhibitors of fructose-1,6-bisphosphatase (F16Bpase) are reported. The compounds have a different SAR as inhibitors of F16Bpase than anilinoquinazolines previously reported. Selective inhibition of F16Bpase can be attained through the addition of appropriate polar functional groups at the quinazoline 2-position, thus separating the F16Bpase inhibitory activity from the epidermal growth factor receptor tyrosine kinase inhibitory activity previously observed with similar structures. The compounds have been found to bind at a symmetry-repeated novel allosteric site at the subunit interface of the enzyme. Inhibition is brought about by binding to a loop comprised of residues 52-72, preventing the necessary participation of these residues in the assembly of the catalytic site. Mutagenesis studies have identified the key amino acid residues in the loop that are required for inhibitor recognition and binding.
机译：报道了一系列新颖的苯胺喹唑啉类化合物作为果糖-1,6-双磷酸酶（F16Bpase）的变构抑制剂，其合成与体外构效关系（SAR）。该化合物作为F16Bpase抑制剂的SAR与先前报道的苯胺喹唑啉不同。可以通过在喹唑啉2位上添加适当的极性官能团来实现对F16Bpase的选择性抑制，从而将F16Bpase抑制活性与先前在相似结构下观察到的表皮生长因子受体酪氨酸激酶抑制活性分开。已经发现这些化合物在酶的亚基界面处的对称重复的新变构位点处结合。通过与由残基52-72组成的环结合来实现抑制，从而防止了这些残基在催化位点的组装中的必要参与。诱变研究已经确定了抑制剂识别和结合所需的环中关键氨基酸残基。

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