Interactions between β2-Adrenoceptor Ligands and Membrane: Atomic-Level Insights from Magic-Angle Spinning NMR,Journal of Medicinal Chemistry

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Interactions between β2-Adrenoceptor Ligands and Membrane: Atomic-Level Insights from Magic-Angle Spinning NMR
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2017-08-04 00:00:00 , DOI: 10.1021/acs.jmedchem.7b00205
Si Yan ₁ , Duncan E. Shaw ₁ , Linhong Yang ₁ , David A. Sandham ₁ , Mark P. Healy ₁ , John Reilly ₁ , Bing Wang ₁

Affiliation

To understand the relationship between structural properties of the β2-adrenoceptor ligands and their interactions with membranes, we have investigated the location and distribution of five β2 agonists with distinct clinical durations and onsets of action (indacaterol, two indacaterol analogues, salmeterol and formoterol) in monounsaturated model membranes using magic angle spinning NMR to measure these interactions through both ¹H nuclear Overhauser enhancement (NOE) and paramagnetic relaxation enhancement (PRE) techniques. The hydrophilic aromatic groups of all five β2 agonists show maximum distribution in the lipid/water interface, but distinct location and dynamic behavior were observed for the lipophilic aromatic rings. Our study elucidates at atomic level that the hydrophobicity and substitution geometry of lipophilic groups play important roles in compound–lipid interactions.

中文翻译：

β2-肾上腺素受体配体与膜之间的相互作用：魔角旋转NMR的原子能级见解

为了了解β2-肾上腺素受体配体的结构性质及其与膜相互作用之间的关系，我们研究了五种具有不同临床持续时间和作用发作的β2激动剂（茚达特罗，两种茚达特罗类似物，沙美特罗和福莫特罗）的位置和分布。使用魔角旋转NMR测量单不饱和模型膜的相互作用，通过¹H核Overhauser增强（NOE）和顺磁弛豫增强（PRE）技术。所有五个β2激动剂的亲水性芳族基团在脂质/水界面中显示出最大的分布，但是亲脂性芳族环则观察到明显的位置和动力学行为。我们的研究在原子水平上阐明了亲脂基团的疏水性和取代几何结构在化合物与脂质的相互作用中起着重要作用。

更新日期：2017-08-05

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