• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Chemistry: A European journal >Cyclopropane-Based Peptidomimetics Mimicking Wide-Ranging Secondary Structures of Peptides: Conformational Analysis and Their Use in Rational Ligand Optimization
【24h】

Cyclopropane-Based Peptidomimetics Mimicking Wide-Ranging Secondary Structures of Peptides: Conformational Analysis and Their Use in Rational Ligand Optimization

机译：基于环丙烷的肽模拟肽的庞大肽：构象分析及其在理性配体优化中的应用

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

Detailed conformational analyses of our previously reported cyclopropane-based peptidomimetics and conformational analysis-driven ligand optimization are described. Computational calculations and X-ray crystallography showed that the characteristic features of cyclopropane function effectively to constrain the molecular conformation in a three-dimensionally diverse manner. Subsequent principal component analysis revealed that the diversity covers the broad chemical space filled by peptide secondary structures in terms of both main-chain and side-chain conformations. Based on these analyses, a lead stereoisomer targeting melanocortin receptors was identified, and its potency and subtype selectivity were improved by further derivatization. The presented strategy is effective not only for designing non-peptidic ligands from a peptide ligand but also for the rational optimization of these ligands based on the plausible target-binding conformation without requiring the threedimensional structural information of the target and its peptide ligands.
机译：描述了我们先前报道的基于环丙烷的拟肽模拟物和构象分析驱动的配体优化的详细构象分析。计算计算和X射线晶体表明，环丙烷功能的特征有效地以三维不同的方式约束分子构象。随后的主要成分分析显示，在主链和侧链构象方面，多样性覆盖肽二次结构的广泛化学空间。基于这些分析，鉴定了靶向黑素素受体的铅立体异构体，通过进一步衍生化改善了其效力和亚型选择性。呈现的策略不仅用于设计来自肽配体的非肽型配体，而且还用于基于可合理的靶结合构象来实现这些配体的合理优化，而不需要靶标和其肽配体的三重结构信息。

著录项

  • 来源
    《Chemistry: A European journal》 |2017年第13期|共10页
  • 作者

    Akira Mizuno; Tomoshi Kameda; Tomoki Kuwahara; Hideyuki Endoh; Yoshihiko Ito; Shizuo Yamada; Kimiko Hasegawa; Akihito Yamano; Mizuki Watanabe; Mitsuhiro Arisawa; Satoshi Shuto;

  • 作者单位

    Faculty of Pharmaceutical Sciences Hokkaido University Kita-12 Nishi-6 Kita-ku Sapporo Hokkaido 060-0812 (Japan);

    Computational Biology Research Center National Institute of Advanced Industrial Science and Technology 2-4-7 Aomi Koutou-ku Tokyo 135-0064 (Japan);

    Faculty of Pharmaceutical Sciences Hokkaido University Kita-12 Nishi-6 Kita-ku Sapporo Hokkaido 060-0812 (Japan);

    Faculty of Pharmaceutical Sciences Hokkaido University Kita-12 Nishi-6 Kita-ku Sapporo Hokkaido 060-0812 (Japan);

    School of Pharmaceutical Sciences University of Shizuoka Yata Suruga-ku Shizuoka Shizuoka 422-8526 (Japan);

    School of Pharmaceutical Sciences University of Shizuoka Yata Suruga-ku Shizuoka Shizuoka 422-8526 (Japan);

    Rigaku Corporation Application Laboratories 3-9-12 Matsubara-cho Akishima Tokyo 196-8666 (Japan);

    Rigaku Corporation Application Laboratories 3-9-12 Matsubara-cho Akishima Tokyo 196-8666 (Japan);

    Faculty of Pharmaceutical Sciences Hokkaido University Kita-12 Nishi-6 Kita-ku Sapporo Hokkaido 060-0812 (Japan);

    Faculty of Pharmaceutical Sciences Hokkaido University Kita-12 Nishi-6 Kita-ku Sapporo Hokkaido 060-0812 (Japan);

    Faculty of Pharmaceutical Sciences Hokkaido University Kita-12 Nishi-6 Kita-ku Sapporo Hokkaido 060-0812 (Japan);

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 应用化学;
  • 关键词

    chemical space; conformation analysis; drug design; peptidomimetics; three-dimensional structural diversity;

    机译：化学空间;构象分析;药物设计;拟肌瘤;三维结构多样性;

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