Proteome Integral Solubility Alteration: A High-Throughput Proteomics Assay for Target Deconvolution
Proteome Integral Solubility Alteration: A High-Throughput Proteomics Assay for Target Deconvolution
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DOI：
10.1021/acs.jproteome.9b00500
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发表时间：
2019-11-01
影响因子：
4.4
通讯作者：
Zubarev, Roman A.
中科院分区：
文献类型：
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作者：
Gaetani, Massimiliano;Sabatier, Pierre;Zubarev, Roman A.
各种试剂，包括药物以及非分子刺激物，诱导细胞裂解物、活细胞和生物体中蛋白质的物理化学性质的改变。这些变化可以通过应用稳定性和溶解度调节因子（如升高的温度）在不同程度上进行探测。作为变化的第二维度，可以使用药物浓度或药剂强度/浓度。与将曲线拟合到在不同温度和药物浓度下获得的蛋白质溶解度数据的标准方法相比，蛋白质组积分溶解度改变（比萨）测定法在这种方案中对于无限数量的因子变化点将分析通量增加1至2个数量级。化合物和生物材料的消耗在比萨中以相同的因子减少。我们设想在化学生物学和药物开发中广泛使用比萨方法。
Various agents, including drugs as well as nonmolecular stimuli, induce alterations in the physicochemical properties of proteins in cell lysates, living cells, and organisms. These alterations can be probed by applying a stability- and solubility-modifying factor, such as elevated temperature, to a varying degree. As a second dimension of variation, drug concentration or agent intensity/concentration can be used. Compared to standard approaches where curves are fitted to protein solubility data acquired at different temperatures and drug concentrations, Proteome Integral Solubility Alteration (PISA) assay increases the analysis throughput by 1 to 2 orders of magnitude for an unlimited number of factor variation points in such a scheme. The consumption of the compound and biological material decreases in PISA by the same factor. We envision widespread use of the PISA approach in chemical biology and drug development.