...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochimica et biophysica acta: BBA: International journal of biochemistry, biophysics and molecular biololgy. Proteins and Proteomics >Energy based pharmacophore mapping of HDAC inhibitors against class i HDAC enzymes
【24h】

Energy based pharmacophore mapping of HDAC inhibitors against class i HDAC enzymes

机译：HDAC抑制剂针对I类HDAC酶的基于能量的药效团定位

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

Histone deacetylases (HDACs) are important class of enzymes that deacetylate the ??-amino group of the lysine residues in the histone tails to form a closed chromatin configuration resulting in the regulation of gene expression. Inhibition of these HDACs enzymes have been identified as one of the promising approaches for cancer treatment. The type-specific inhibition of class I HDAC enzymes is known to elicit improved therapeutic effects and thus, the search for promising type-specific HDAC inhibitors compounds remains an ongoing research interest in cancer drug discovery. Several different strategies are employed to identify the features that could identify the isoform specificity factors in these HDAC enzymes. This study combines the insilico docking and energy-optimized pharmacophore (e-pharmacophore) mapping of several known HDACi's to identify the structural variants that are significant for the interactions against each of the four class I HDAC enzymes. Our hybrid approach shows that all the inhibitors with at least one aromatic ring in their linker regions hold higher affinities against the target enzymes, while those without any aromatic rings remain as poor binders. We hypothesize the e-pharmacophore models for the HDACi's against all the four Class I HDAC enzymes which are not reported elsewhere. The results from this work will be useful in the rational design and virtual screening of more isoform specific HDACi's against the class I HDAC family of proteins. ? 2012 Elsevier B.V. All rights reserved.
机译：组蛋白脱乙酰基酶（HDACs）是一类重要的酶，它们使组蛋白尾巴中赖氨酸残基的β-氨基脱乙酰基，形成封闭的染色质构型，从而调节基因表达。这些HDACs酶的抑制已被确定为癌症治疗的有前途的方法之一。已知对I类HDAC酶的类型特异性抑制可引起改善的治疗效果，因此，寻找有希望的类型特异性HDAC抑制剂化合物仍是癌症药物发现中正在进行的研究兴趣。采用几种不同的策略来鉴定可以鉴定这些HDAC酶中同工型特异性因子的特征。这项研究结合了几种已知的HDACi的分子对接和能量优化的药效基团（e-pharmacophore）作图，以鉴定对四种I类HDAC酶中的每一种相互作用均具有重要意义的结构变异。我们的杂交方法表明，所有在其连接子区域具有至少一个芳香环的抑制剂对目标酶都具有较高的亲和力，而那些没有任何芳香环的抑制剂则保持较弱的结合力。我们假设针对所有四种I类HDAC酶的HDACi的电子药效团模型，这在其他地方未见报道。这项工作的结果将有助于针对I类HDAC蛋白质家族对更多同工型特异性HDACi进行合理设计和虚拟筛选。 ？ 2012 Elsevier B.V.保留所有权利。

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