Tilting and Tumbling in Transmembrane Anion Carriers: Activity Tuning through n-Alkyl Substitution.
Tilting and Tumbling in Transmembrane Anion Carriers: Activity Tuning through n-Alkyl Substitution.
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DOI：
10.1002/chem.201504057
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发表时间：
2016-02
影响因子：
4.3
通讯作者：
Davis, Anthony P.
中科院分区：
文献类型：
--
作者：
Edwards, Sophie J.;Marques, Igor;Dias, Christopher M.;Tromans, Robert A.;Lees, Nicholas R.;Felix, Vitor;Valkenier, Hennie;Davis, Anthony P.
合成载体（阴离子载体）的阴离子传输有望在医学应用中发挥作用，尤其是囊性纤维化的治疗。在决定载体活性的因素中，烷基的大小和分布被证明非常重要。在此，我们描述了一系列二硫脲基十氢化萘阴离子载体，其中一个面上的烷基取代基在双碳步骤中从 C0 到 C10 变化。随着链长的增加，活性先增加后减少，在 C6 处达到峰值。分子动力学模拟表明，转运氯复合物在接近膜-水界面时会释放氯。然后，自由转运蛋白停留在界面处，采用取决于烷基取代基的方向。如果防止氯化物释放，则复合物的位置类似。较长的链使结合位点远离界面，可能释放转运蛋白或复合物以穿过膜。然而，太长的链也会通过抑制磷脂双层内的运动，尤其是重新定向来减慢运输。
Anion transport by synthetic carriers (anionophores) holds promise for medical applications, especially the treatment of cystic fibrosis. Among the factors which determine carrier activity, the size and disposition of alkyl groups is proving remarkably important. Herein we describe a series of dithioureidodecalin anionophores, in which alkyl substituents on one face are varied from C0 to C10 in two‐carbon steps. Activities increase then decrease as the chain length grows, peaking quite sharply at C6. Molecular dynamics simulations showed the transporter chloride complexes releasing chloride as they approach the membrane‐aqueous interface. The free transporter then stays at the interface, adopting an orientation that depends on the alkyl substituent. If chloride release is prevented, the complex is positioned similarly. Longer chains tilt the binding site away from the interface, potentially freeing the transporter or complex to move through the membrane. However, chains which are too long can also slow transport by inhibiting movement, and especially reorientation, within the phospholipid bilayer.
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影响因子：
5.5
作者：
Goetz, Andreas W.;Williamson, Mark J.;Xu, Dong;Poole, Duncan;Le Grand, Scott;Walker, Ross C.
通讯作者：
Walker, Ross C.
影响因子：
16.6
作者：
Jentzsch, Andreas Vargas;Emery, Daniel;Matile, Stefan
通讯作者：
Matile, Stefan
影响因子：
16.6
作者：
Koulov, AV;Lambert, TN;Davis, AP
通讯作者：
Davis, AP
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML
DOI：
10.1021/jp8001614
发表时间：
2008-07-31
期刊：
The journal of physical chemistry. B
影响因子：
--
作者：
Joung IS;Cheatham TE 3rd
通讯作者：
Cheatham TE 3rd