Design and Synthesis of Labystegines, Hybrid Iminosugars from LAB and Calystegine, as Inhibitors of Intestinal alpha-Glucosidases: Binding Conformation and Interaction for ntSI
文献类型：期刊论文
| 作者 | Kato, Atsushi1; Zhang, Zhao-Lan2; Wang, Hong-Yao2; Jia, Yue-Mei2; Yu, Chu-Yi2; Kinami, Kyoko1; Hirokami, Yuki1; Tsuji, Yutaro1; Adachi, Isao1; Nash, Robert J.3 |
| 刊名 | JOURNAL OF ORGANIC CHEMISTRY
 |
| 出版日期 | 2015-05-01 |
| 卷号 | 80期号:9页码:4501-4515 |
| 英文摘要 | This paper identifies the required configuration and orientation of alpha-glucosidase inhibitors, miglitol, alpha-1-C-butyl-DNJ, and alpha-1-C-butyl-LAB for binding to ntSI (isomaltase). Molecular dynamics (MD) calculations suggested that the flexibility around the keyhole of ntSI is lower than that of ctSI (sucrase). Furthermore, a molecular-docking study revealed that a specific binding orientation with a CH-pi interaction (Trp370 and Phe648) is a requirement for achieving a strong affinity with ntSI. On the basis of these results, a new class of nortropane-type iminosugars, labystegines, hybrid iminosugars of LAB and calystegine, have been designed and synthesized efficiently from sugar-derived cyclic nitrones with intramolecular 1,3-dipolar cycloaddition or samarium iodide catalyzed reductive coupling reaction as the key step. Biological evaluation showed that our newly designed 3(S)-hydroxy labystegine (6a) inherited the selectivity against intestinal alpha-glucosidases from LAB, and its inhibition potency was 10 times better than that of miglitol. Labystegine, therefore, represents a promising new class of nortropane-type iminosugar for improving postprandial hyperglycemia. |
| 收录类别 | SCI |
| 语种 | 英语 |
| 公开日期 | 2015-11-02 |
| 源URL | [http://ir.iccas.ac.cn/handle/121111/28074]  |
| 专题 | 化学研究所_分子识别与功能实验室 |
| 作者单位 | 1.Toyama Univ, Dept Hosp Pharm, Toyama 9300194, Japan 2.Chinese Acad Sci, BNLMS, CAS Key Lab Mol Recognit & Funct, Inst Chem, Beijing 100190, Peoples R China 3.Phytoquest Ltd, Inst Biol Environm & Rural Sci, Plas Gogerddan, Aberystwyth SY23 3EB, Ceredigion, Wales 4.Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 3TA, England 5.Jiangxi Normal Univ, Natl Engn Res Ctr Carbohydrate Synth, Nanchang 330022, Peoples R China 6.Kitasato Univ, Sch Pharmaceut Sci, Tokyo 1088641, Japan |
| 推荐引用方式 GB/T 7714 | Kato, Atsushi,Zhang, Zhao-Lan,Wang, Hong-Yao,et al. Design and Synthesis of Labystegines, Hybrid Iminosugars from LAB and Calystegine, as Inhibitors of Intestinal alpha-Glucosidases: Binding Conformation and Interaction for ntSI[J]. JOURNAL OF ORGANIC CHEMISTRY,2015,80(9):4501-4515. |
| APA | Kato, Atsushi.,Zhang, Zhao-Lan.,Wang, Hong-Yao.,Jia, Yue-Mei.,Yu, Chu-Yi.,...&Hirono, Shuichi.(2015).Design and Synthesis of Labystegines, Hybrid Iminosugars from LAB and Calystegine, as Inhibitors of Intestinal alpha-Glucosidases: Binding Conformation and Interaction for ntSI.JOURNAL OF ORGANIC CHEMISTRY,80(9),4501-4515. |
| MLA | Kato, Atsushi,et al."Design and Synthesis of Labystegines, Hybrid Iminosugars from LAB and Calystegine, as Inhibitors of Intestinal alpha-Glucosidases: Binding Conformation and Interaction for ntSI".JOURNAL OF ORGANIC CHEMISTRY 80.9(2015):4501-4515. |
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来源：化学研究所
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