• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>RSC Advances >Structure activity related, mechanistic, and modeling studies of gallotannins containing a glucitol-core and alpha-glucosidase
【24h】

Structure activity related, mechanistic, and modeling studies of gallotannins containing a glucitol-core and alpha-glucosidase

机译：结构活动相关，机械和含有葡糖酚核苷酸的加拉突蛋白的建模研究和α-葡糖苷酶

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

Gallotannins containing a glucitol core, which are only produced by members of the maple (Acer) genus, are more potent alpha-glucosidase inhibitors than the clinical drug, acarbose. While this activity is influenced by the number of substituents on the glucitol core (e.g. more galloyl groups leads to increased activity), the mechanisms of inhibitory action are not known. Herein, we investigated ligand-enzyme interactions and binding mechanisms of a series of 'glucitol-core containing gallotannins (GCGs)' against the a-glucosidase enzyme. The GCGs included ginnalins A, B and C (containing two, one, and one galloyl/s, respectively), maplexin F (containing 3 galloyls) and maplexin J (containing 4 galloyls). All of the GCGs were noncompetitive inhibitors of alpha-glucosidase and their interactions with the enzyme were further explored using biophysical and spectroscopic measurements. Thermodynamic parameters (by isothermal titration calorimetry) revealed a 1 : 1 binding ratio between GCGs and alpha-glucosidase. The binding regions between the GCGs and alpha-glucosidase, probed by a fluorescent tag, 1,1'-bis(4-anilino-5-naphthalenesulfonic acid), revealed that the GCGs decreased the hydrophobic surface of the enzyme. In addition, circular dichroism analyses showed that the GCGs bind to alpha-glucosidase and lead to loss of the secondary alpha-helix structure of the protein. Also, molecular modeling was used to predict the binding site between the GCGs and the alpha-glucosidase enzyme. This is the first study to evaluate the mechanisms of inhibitory activities of gallotannins containing a glucitol core on alpha-glucosidase.
机译：含有葡萄糖醇核心棓单宁，其仅由枫木（宏基）属的成员产生的，是更有效的α-糖苷酶抑制剂比临床药物，阿卡波糖。虽然这种活性是通过在葡萄糖醇核心（例如更多个棓酰基导致增加的活性）的取代基的数目的影响，抑制作用的机制尚不清楚。在本文中，我们研究了配体 - 酶相互作用等一系列针对α-葡糖苷酶“含有葡萄糖醇核棓单宁（GCGs）”的结合机制。所包括的GCGs ginnalins A，B和C（分别为两个，一个，和一个没食子酰基/ s时，含有），maplexin F（含有3个galloyls）和maplexinĴ（含有4个galloyls）。所有GCGs的是α-葡糖苷酶的非竞争性抑制剂以及它们与酶使用生物物理和光谱测量进一步探讨的相互作用。热力学参数（由等温滴定量热法）显示一个1：GCGs和α-葡糖苷酶1之间的结合比率。的GCGs和α-葡糖苷酶之间的结合区域，由荧光标签探测，1,1'-双（4-苯胺基-5-萘磺酸），发现该GCGs降低酶的疏水性表面。此外，圆二色性分析表明，GCGs结合α-葡糖苷酶，并导致蛋白质的二级α螺旋结构的损失。此外，分子建模来预测GCGs和α-葡糖苷酶的酶之间的结合位点。这是第一个研究，以评估含有对α-葡萄糖苷酶一葡萄糖醇芯棓单宁的抑制活性的机制。

著录项

  • 来源
    《RSC Advances》 |2015年第130期|共12页
  • 作者

    Ma Hang; Wang Ling; Niesen Daniel B.; Cai Ang; Cho Bongsup P.; Tan Wen; Gu Qiong; Xu Jun; Seeram Navindra P.;

  • 作者单位

    Univ Rhode Isl Coll Pharm Dept Biomed &

    Pharmaceut Sci Kingston RI 02881 USA;

    Sun Yat Sen Univ Sch Pharmaceut Sci Guangzhou 510006 Guangdong Peoples R China;

    Univ Rhode Isl Coll Pharm Dept Biomed &

    Pharmaceut Sci Kingston RI 02881 USA;

    Univ Rhode Isl Coll Pharm Dept Biomed &

    Pharmaceut Sci Kingston RI 02881 USA;

    Univ Rhode Isl Coll Pharm Dept Biomed &

    Pharmaceut Sci Kingston RI 02881 USA;

    S China Univ Technol Sch Biosci &

    Bioengn Preincubator Innovat Drugs &

    Med Guangzhou 510006 Guangdong Peoples R China;

    Sun Yat Sen Univ Sch Pharmaceut Sci Guangzhou 510006 Guangdong Peoples R China;

    Sun Yat Sen Univ Sch Pharmaceut Sci Guangzhou 510006 Guangdong Peoples R China;

    Univ Rhode Isl Coll Pharm Dept Biomed &

    Pharmaceut Sci Kingston RI 02881 USA;

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

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