Direct interaction of ONO-5046 with human neutrophil elastase through H-1 NMR and molecular docking
文献类型：期刊论文
| 作者 | Feng, Li2; Zhu, Weiliang1 ; Huang, Cheng2; Li, Yiming2
|
| 刊名 | INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
 |
| 出版日期 | 2012-10 |
| 卷号 | 51期号:3页码:196-200 |
| 关键词 | Human neutrophil elastase ONO-5046 Spin-relaxation rate Molecular rotational correlation time Molecular docking |
| ISSN号 | 0141-8130 |
| DOI | 10.1016/j.ijbiomac.2012.04.023 |
| 文献子类 | Article |
| 英文摘要 | Human neutrophil elastase (HNE) has been implicated as a major contributor in the pathogenesis of diseases, such as pulmonary emphysema, acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and other inflammatory diseases. Therefore, searching for appropriate and potential human neutrophil elastase inhibitors (HNEI) that would restore the balance between the free enzyme and the endogenous inhibitors would be of therapeutic interest. ONO-5046 is the first specific HNEI to improve respiratory function and protect lung tissues against various lung injuries. However, the mechanism of ONO-5046 to HNE is still unclear. In this study, the binding properties of ONO-5046 were investigated through H-1 NMR, molecular docking, and bioassay methods to understand the effect of ONO-5046 to HNE. The proton spin-lattice relaxation rate and molecular rotational correlation time results indicated that ONO-5046 has higher affinity with HNE. The molecular docking study showed that ONO-5046 is perfectly matched for the primary enzyme specificity pocket (S1 pocket), and is tightly bound to this pocket of HNE through hydrophobic and hydrogen bonding interactions. The results of both methods were validated through analysis of the FINE inhibitory activity bioassay of ONO-5046 with an IC50 value of 87.05 nM. Our data suggested that ONO-5046 could bind to HNE through direct interaction, and that molecular docking and NMR methods are valid approaches to survey new HNEI. (C) 2012 Elsevier B.V. All rights reserved. |
| WOS关键词 | ACUTE LUNG INJURY ; INHIBITOR ; RELAXATION ; SIVELESTAT ; LEUKOCYTE ; DERIVATIVES ; DISCOVERY ; ALBUMIN |
| 资助项目 | National Science and Technology Major Project of China[2009ZX09311-003] ; program for Professors of Special Appointment (Eastern Scholar) in Shanghai Institutions of Higher Learning[00000000] ; "XinLin" scholars and outstanding team training plan of SHUTCM[00000000] ; Program for Shanghai Key Discipline Establishment of TCM Pharmaceutics[J50302] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry ; Polymer Science |
| 语种 | 英语 |
| WOS记录号 | WOS:000307134200003 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277938]  |
| 专题 | 天然药物化学研究室 药物发现与设计中心 |
| 通讯作者 | Li, Yiming |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Feng, Li,Zhu, Weiliang,Huang, Cheng,et al. Direct interaction of ONO-5046 with human neutrophil elastase through H-1 NMR and molecular docking[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,2012,51(3):196-200. |
| APA | Feng, Li,Zhu, Weiliang,Huang, Cheng,&Li, Yiming.(2012).Direct interaction of ONO-5046 with human neutrophil elastase through H-1 NMR and molecular docking.INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,51(3),196-200. |
| MLA | Feng, Li,et al."Direct interaction of ONO-5046 with human neutrophil elastase through H-1 NMR and molecular docking".INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES 51.3(2012):196-200. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。