Affinity screening using competitive binding with fluorine-19 hyperpolarized ligands.
Affinity screening using competitive binding with fluorine-19 hyperpolarized ligands.
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DOI：
10.1002/anie.201411424
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发表时间：
2015-04-13
影响因子：
16.6
通讯作者：
Hilty, Christian
中科院分区：
文献类型：
--
作者：
Kim, Yaewon;Hilty, Christian
氟-19 NMR和超极化形成了药物筛选的强大组合。在与选定的氟化报告配体的竞争平衡下，使用单扫描Carr-Purcell-Meiboom-Gill（CPMG）实验可测量其他感兴趣配体的解离常数（KD），而不需要滴定。该方法通过表征具有不同亲和力的丝氨酸蛋白酶胰蛋白酶的三种配体的结合来证明。蒙特卡罗模拟表明，最高的准确度时，获得约一半的绑定报告配体被取代的结合竞争。这样的条件可以在广泛的亲和力范围内实现，从而允许在已知针对感兴趣的结合口袋的单个氟化配体时快速筛选非氟化化合物。
Fluorine-19 NMR and hyperpolarization form a powerful combination for drug screening. Under a competitive equilibrium with a selected fluorinated reporter ligand, the dissociation constant (KD) of other ligands of interest is measurable using a single-scan Carr-Purcell-Meiboom-Gill (CPMG) experiment, without the need for a titration. This method is demonstrated by characterizing the binding of three ligands with different affinities for the serine protease trypsin. Monte Carlo simulations show that the highest accuracy is obtained when about one-half of the bound reporter ligand is displaced in the binding competition. Such conditions can be achieved over a wide range of affinities, allowing for rapid screening of non-fluorinated compounds when a single fluorinated ligand to the binding pocket of interest is known.
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影响因子：
15
作者：
Dalvit, C;Mongelli, N;Kümmerle, R
通讯作者：
Kümmerle, R
影响因子：
2.9
作者：
Chen, Ning;Zou, Jin;Wang, Siming;Ye, Yiming;Huang, Yun;Gadda, Giovanni;Yang, Jenny J.
通讯作者：
Yang, Jenny J.
影响因子：
4.3
作者：
Heath, RE;Dykes, GM;Smith, DK
通讯作者：
Smith, DK
影响因子：
3.3
作者：
Leggett, James;Hunter, Robert;Koeckenberger, Walter
通讯作者：
Koeckenberger, Walter
影响因子：
3.4
作者：
Buratto R;Bornet A;Milani J;Mammoli D;Vuichoud B;Salvi N;Singh M;Laguerre A;Passemard S;Gerber-Lemaire S;Jannin S;Bodenhausen G
通讯作者：
Bodenhausen G