Understanding the Interaction between Valsartan and Detergents by NMR Techniques and Molecular Dynamics Simulation
文献类型：期刊论文
| 作者 | Cao, Chenyu1,2; Mao, Jiezhen1; Li, Fang3; Yang, Minghui1; He, Hongqing1 ; Jiang, Ling1; Liu, Maili1
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| 刊名 | JOURNAL OF PHYSICAL CHEMISTRY B
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| 出版日期 | 2012-06-28 |
| 卷号 | 116期号:25页码:7470-7478 |
| 合作状况 | 国内 |
| 英文摘要 | Valsartan (VST) is one of the Angiotensin II receptor antagonists, which is widely used in clinical hypertension treatment. It is believed that VST incorporates into biological membranes before it binds to AT(1) receptor. Herein the interactions between VST and detergents, mimicking the membrane environment, were investigated by using nuclear magnetic resonance (NMR) techniques and molecular dynamics (MD) simulation. We observed that VST has two conformers (trans and cis) exchanging slowly in DPC (dodecyl-phosphocholine) micelles, a widely used detergent. The changes of chemical shifts, relaxation rates, and self-diffusion coefficients of VST protons indicate that both conformers have strong interactions with DPC. NOE cross peaks and MD simulation reveal that DPC interacts with VST not only through the hydrophobic lipid chain, but also the hydrophilic headgroup, locating VST at the charged headgroup and upper part of the micelles. Our results are in good agreement with the Raman spectroscopic studies of VST in the DPPC (dipalmitoylphosphatidylcholine) bilayers by Potamitis et al. (Biochim. Biophys. Acta. 2011). The concentration ratio of trans over cis conformers is 0.94, showing that two conformers have the same affinities with the detergent, which is significantly smaller than our previous results obtained in SDS (sodium dodecyl sulfate) micelles. MD simulation suggested that the cis conformer has slightly lower binding free energy than the trans conformer when interacting with DPC. The conformational change of VST was further investigated in two detergents, CTAB (hexadecyltrimethylammonium bromide) and Tween-20 (polysorbate 20). Ratios of conformer A and B in the presence of detergents are in the order of DPC, CTAB < Tween-20 < SDS, which is correlated with the charge characters of their head groups. NMR investigations and MD simulations indicate that the electrostatic interaction plays an essential role in the binding process of VST with detergents, and the hydrophobic interaction influences the packing of the drug in the micelles. These results may be of help in understanding delivery processes of sartan drugs in cell membranes. |
| WOS标题词 | Science & Technology ; Physical Sciences |
| 类目[WOS] | Chemistry, Physical |
| 研究领域[WOS] | Chemistry |
| 关键词[WOS] | ANGIOTENSIN-II RECEPTOR ; AT(1) ANTAGONIST LOSARTAN ; DODECYL-SULFATE MICELLE ; RESONANCE-SPECTROSCOPY ; MEMBRANES ; BILAYERS ; DIFFUSION ; BINDING ; SURFACE ; FIELD |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000305769700010 |
| 公开日期 | 2015-07-14 |
| 版本 | 出版稿 |
| 源URL | [http://ir.wipm.ac.cn/handle/112942/1693]  |
| 专题 | 武汉物理与数学研究所_磁共振基础研究部 |
| 作者单位 | 1.Chinese Acad Sci, Wuhan Ctr Magnet Resonance, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan 430071, Peoples R China 2.Huazhong Univ Sci & Technol, Sch Life Sci & Technol, Wuhan 430074, Peoples R China 3.Cent China Normal Univ, Dept Chem, Wuhan 430079, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cao, Chenyu,Mao, Jiezhen,Li, Fang,et al. Understanding the Interaction between Valsartan and Detergents by NMR Techniques and Molecular Dynamics Simulation[J]. JOURNAL OF PHYSICAL CHEMISTRY B,2012,116(25):7470-7478. |
| APA | Cao, Chenyu.,Mao, Jiezhen.,Li, Fang.,Yang, Minghui.,He, Hongqing.,...&Liu, Maili.(2012).Understanding the Interaction between Valsartan and Detergents by NMR Techniques and Molecular Dynamics Simulation.JOURNAL OF PHYSICAL CHEMISTRY B,116(25),7470-7478. |
| MLA | Cao, Chenyu,et al."Understanding the Interaction between Valsartan and Detergents by NMR Techniques and Molecular Dynamics Simulation".JOURNAL OF PHYSICAL CHEMISTRY B 116.25(2012):7470-7478. |
入库方式： OAI收割
来源：武汉物理与数学研究所
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