Rapid screening of binding constants by calibrated competitive 1H NMR spectroscopy
Rapid screening of binding constants by calibrated competitive 1H NMR spectroscopy
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DOI：
10.1002/chem.200390094
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发表时间：
2003-02-17
影响因子：
4.3
通讯作者：
Smith, DK
中科院分区：
文献类型：
--
作者：
Heath, RE;Dykes, GM;Smith, DK
已经开发出一种校准的竞争性 NMR 方法，适用于快速筛选结合常数。该方法涉及受体-底物结合事件的初始表征，其中给定受体（校准物）的 H-1 NMR 谱在一定浓度范围内被感兴趣的底物修改。对于所有随后的“未知”受体，然后通过使用竞争测定（在校准受体存在下）通过测量单个标准 H-1 NMR 谱来确定 K-a 值。这使得能够快速评估潜在受体库的识别特性。只有校准受体需要具有 NMR 活性，而推定受体库则需要具有 NMR 活性。以及基材。可以是 NMR 无声的。该方法假设形成 1:1 化学计量的复合物。为了证明这种方法，研究了许多冠醚型化合物与 K-离子的结合。使用这种方法获得的结合强度与文献中的结合强度的比较显示出极好的一致性。我们小组最近合成的一系列新化合物也经过筛选，以说明这种方法如何快速评估结合能力。该方法作为快速优化结合强度的手段，对于组合受体/底物设计和超分子化学领域的化学家具有重要意义。
A calibrated competitive NMR method has been developed that is appropriate for the rapid screening of binding constants. This method involves the initial characterisation of a receptor-substrate binding event for which the H-1 NMR spectrum of a given receptor (calibrant) is modified by the substrate of interest at a range of concentrations. For all subsequent "unknown" receptors, K-a values are then determined by using a competition assay (in the presence of the calibrant receptor) by measuring a single standard H-1 NMR spectrum. This enables a rapid assessment of the recognition properties of a library of potential receptors. Only the calibrant receptor needs to be NMR active, while the library of putative receptors. as well as the substrate. can be NMR silent. This method assumes the formation of complexes of 1:1 stoichiometry. To demonstrate this methodology, the binding of a number of crown ether type compounds with K- ions has been studied. Comparison of the binding strengths obtained by using this approach with those in the literature shows excellent agreement. A range of new compounds that have recently been synthesised within our group has also been screened in order to illustrate how this approach can rapidly assess binding ability. This method has significance for chemists working in the fields of combinatorial receptor/substrate design and supramolecular chemistry as a means of rapid optimisation of binding strength.