Sequence mapping of epoxide adducts in human hemoglobin with LC-tandem MS and the salsa algorithm

被引:37
作者
Badghisi, H
Liebler, DC [1 ]
机构
[1] Univ Arizona, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA
[2] Univ Arizona, SW Environm Hlth Sci Ctr, Tucson, AZ 85721 USA
[3] Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA
关键词
D O I
10.1021/tx015589+
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The rapid development and integration of liquid chromatography-tandem mass spectrometry (LC-MS-MS) has enabled the high-throughput identification of proteins and driven the expanding field of proteomics. LC-MS-MS also offers an attractive general approach to the analysis of xenobiotic adducts on proteins. The aim of this study was to examine the combined use of LC-MS-MS and the SALSA algorithm as a general approach to map xenobiotic adducts on proteins at the level of amino acid sequence. Hemoglobin (Hb) adducts are commonly used as biomarkers for exposure to environmental toxicants. Human Hb was incubated with styrene oxide, ethylene oxide, and butadiene dioxide (40 mM) to form adducts, digested with trypsin and analyzed by LC-MS-MS on a ThermoFinnigan LCQ ion trap MS instrument. Data-dependent scanning was used for acquisition of MS-MS spectra. The SALSA algorithm was used to detect MS-MS spectra of native and modified Hb peptides. The adducted sites identified are the N-terminal valines of both Hbalpha and Hbbeta, glutamic acid 7, cysteine 93, and histidines 77, 97, and 143 of the beta chain and histidine 45 of the alpha chain. Specific shifts in the b- and y-ion series in MS-MS spectra confirmed the locations of each adduct. This approach offers a means to simultaneously identify multiple Hb adducts resulting from exposures to known or unknown toxicants. Combined application of LC-MS-MS and SALSA thus provides a general means of mapping protein modifications at the level of amino acid sequence.
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页码:799 / 805
页数:7
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