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Chiral probes for α1-AGP reporting by species-specific induced circularly polarised luminescence†
Chemical Science ( IF 8.4 ) Pub Date : 2018-02-19 00:00:00 , DOI: 10.1039/c8sc00482j
Sergey Shuvaev 1, 2, 3, 4 , Elizaveta A. Suturina 4, 5, 6, 7 , Kevin Mason 1, 2, 3, 4 , David Parker 1, 2, 3, 4
Affiliation  

Luminescence spectroscopy has been used to monitor the selective and reversible binding of pH sensitive, macrocyclic lanthanide complexes, [LnL1], to the serum protein α1-AGP, whose concentration can vary significantly in response to inflammatory processes. On binding α1-AGP, a very strong induced circularly-polarised europium luminescence signal was observed that was of opposite sign for human and bovine variants of α1-AGP – reflecting the differences in the chiral environment of their drug-binding pockets. A mixture of [EuL1] and [TbL1] complexes allowed the ratiometric monitoring of α1-AGP levels in serum. Moreover, competitive displacement of [EuL1] from the protein by certain prescription drugs could be monitored, allowing the determination of drug binding constants. Reversible binding of the sulphonamide arm as a function of pH, led to a change of the coordination environment around the lanthanide ion, from twisted square antiprism (TSAP) to a square antiprismatic geometry (SAP), signalled by emission spectral changes and verified by detailed computations and the fitting of NMR pseudocontact shift data in the sulphonamide bound TSAP structure for the Dy and Eu examples. Such analyses allowed a full definition of the magnetic susceptibility tensor for [DyL1].

中文翻译:

手性探针α 1个通过物种特异性诱导的圆偏振发光-AGP报告

发光光谱已被用于监测选择性和pH敏感的,大环镧系元素复合物,的可逆结合[LNL 1 ] α,与血清蛋白1 -AGP,其浓度可以响应于炎性过程显著变化。上α结合1个-AGP,非常强的诱导圆偏振光铕的发光信号中观察到,这是相反符号的对人和牛的α变体1 -AGP -反映在它们的药物结合袋的手性环境中的差异。的混合物[EUL 1 ][TBL 1 ]络合物允许的α比率量度监视1-血清中的AGP水平。此外,可以监测某些处方药从蛋白质中置换[EuL 1 ]的竞争性作用,从而确定药物结合常数。磺酰胺臂作为pH的可逆结合导致镧系元素离子周围的配位环境发生变化,从扭曲方形反棱镜(TSAP)变为方形反棱镜几何形状(SAP),通过发射光谱变化发出信号,并通过详细的验证Dy和Eu实例在磺酰胺键合的TSAP结构中的NMR伪接触位移数据的计算和拟合。这样的分析允许对[DyL 1 ]的磁化率张量进行完整定义。
更新日期:2018-02-19
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