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Characterizing Active Pharmaceutical Ingredient Binding to Human Serum Albumin by Spin-Labeling and EPR Spectroscopy

机译:通过旋转标记和EPR光谱表征与人血清白蛋白结合的活性药物成分

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摘要

Drug binding to human serum albumin (HSA) has been characterized by a spin-labeling and continuous-wave (CW) EPR spectroscopic approach. Specifically, the contribution of functional groups (FGs) in a compound on its albumin-binding capabilities is quantitatively described. Molecules from different drug classes are labeled with EPR-active nitroxide radicals (spin-labeled pharmaceuticals (SLPs)) and in a screening approach CW-EPR spectroscopy is used to investigate HSA binding under physiological conditions and at varying ratios of SLP to protein. Spectral simulations of the CW-EPR spectra allow extraction of association constants (K-A) and the maximum number (n) of binding sites per protein. By comparison of data from 23 SLPs, the mechanisms of drug-protein association and the impact of chemical modifications at individual positions on drug uptake can be rationalized. Furthermore, new drug modifications with predictable protein binding tendency may be envisaged.
机译:结合人血清白蛋白(HSA)的药物已通过自旋标记和连续波(CW)EPR光谱法进行了表征。具体地,定量描述了化合物中的官能团(FG)对其白蛋白结合能力的贡献。来自不同药物类别的分子被EPR活性一氧化氮自由基标记(旋转标记药物(SLP)),在筛选方法中,CW-EPR光谱用于研究在生理条件下以及SLP与蛋白质比率不同时的HSA结合。 CW-EPR光谱的光谱模拟允许提取每个蛋白质的结合常数(K-A)和最大结合位点数(n)。通过比较来自23个SLP的数据,可以使药物-蛋白质结合的机制以及各个位置的化学修饰对药物吸收的影响合理化。此外,可以设想具有可预测的蛋白质结合趋势的新药物修饰。

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