Carlsson Henrik, Rappaport Stephen M, Törnqvist Margareta
Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA 94720, USA.
Department of Environmental Science and Analytical Chemistry, Stockholm University, SE-106 91 Stockholm, Sweden.
High Throughput. 2019 Mar 8;8(1):6. doi: 10.3390/ht8010006.
The reaction products of electrophiles in vivo can be measured as adducts to the abundant proteins, hemoglobin (Hb), and human serum albumin (HSA), in human blood samples. During the last decade, methods for untargeted screening of such adducts, called "adductomics", have used liquid chromatography-mass spectrometry to detect large numbers of previously unknown Hb and HSA adducts. This review presents methodologies that were developed and used in our laboratories for Hb and HSA adductomics, respectively. We discuss critical aspects regarding choice of target protein, sample preparation, mass spectrometry, data evaluation, and strategies for identification of detected unknown adducts. With this review we give an overview of these two methodologies used for protein adductomics and the precursor electrophiles that have been elucidated from the adducts.
体内亲电试剂的反应产物可以在人体血液样本中作为与丰富蛋白质、血红蛋白(Hb)和人血清白蛋白(HSA)的加合物进行测量。在过去十年中,用于此类加合物非靶向筛查的方法,即“加合物组学”,已采用液相色谱 - 质谱法来检测大量先前未知的Hb和HSA加合物。本综述介绍了分别在我们实验室中开发和用于Hb和HSA加合物组学的方法。我们讨论了关于靶蛋白选择、样品制备、质谱分析、数据评估以及检测到的未知加合物鉴定策略等关键方面。通过本综述,我们概述了用于蛋白质加合物组学的这两种方法以及从加合物中阐明的前体亲电试剂。