PMID- 28411555 OWN - NLM STAT- MEDLINE DCOM- 20180403 LR - 20181113 IS - 2213-2317 (Electronic) IS - 2213-2317 (Linking) VI - 12 DP - 2017 Aug TI - Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe. PG - 712-718 LID - S2213-2317(17)30206-9 [pii] LID - 10.1016/j.redox.2017.04.001 [doi] AB - Redox imbalance in cells induces lipid peroxidation and generates a class of highly reactive metabolites known as lipid-derived electrophiles (LDEs) that can modify proteins and affects their functions. Identifying targets of LDEs is critical to understand how such modifications are functionally implicated in oxidative-stress associated diseases. Here we report a quantitative chemoproteomic method to globally profile protein targets and sites modified by LDEs. In this strategy, we designed and synthesized an alkyne-functionalized aminooxy probe to react with LDE-modified proteins for imaging and proteomic profiling. Using this probe, we successfully quantified >4000 proteins modified by 4-hydroxy-2-nonenal (HNE) of high confidence in mammalian cell lysate and combined with a tandem-orthogonal proteolysis activity-based protein profiling (TOP-ABPP) strategy, we identified ~400 residue sites targeted by HNE including reactive cysteines in peroxiredoxins, an important family of enzymes with anti-oxidant roles. Our method expands the toolbox to quantitatively profile protein targets of endogenous electrophiles and the enlarged inventory of LDE-modified proteins and sites will contribute to functional elucidation of cellular pathways affected by oxidative stress. CI - Copyright (c) 2017. Published by Elsevier B.V. FAU - Chen, Ying AU - Chen Y AD - Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University, Beijing 100871, China; College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. FAU - Cong, Yan AU - Cong Y AD - Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University, Beijing 100871, China; College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. FAU - Quan, Baiyi AU - Quan B AD - Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University, Beijing 100871, China; College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. FAU - Lan, Tong AU - Lan T AD - Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University, Beijing 100871, China; College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. FAU - Chu, Xiaoyu AU - Chu X AD - Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University, Beijing 100871, China; College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. FAU - Ye, Zi AU - Ye Z AD - Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. FAU - Hou, Xiaomeng AU - Hou X AD - Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University, Beijing 100871, China; College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. FAU - Wang, Chu AU - Wang C AD - Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University, Beijing 100871, China; College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. Electronic address: chuwang@pku.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170405 PL - Netherlands TA - Redox Biol JT - Redox biology JID - 101605639 RN - 0 (Aldehydes) RN - 0 (Proteome) RN - K1CVM13F96 (4-hydroxy-2-nonenal) SB - IM MH - Aldehydes/*chemistry MH - Binding Sites MH - Chromatography, Liquid MH - HEK293 Cells MH - Humans MH - Lipid Peroxidation MH - Oxidative Stress MH - Protein Processing, Post-Translational MH - Proteome/*chemistry/isolation & purification MH - Proteomics/*methods MH - Tandem Mass Spectrometry PMC - PMC5390668 OTO - NOTNLM OT - 4-hydroxy-2-nonenal OT - Activity-based protein profiling OT - Aminooxy probe OT - Chemoproteomics OT - Lipid-derived electrophile EDAT- 2017/04/16 06:00 MHDA- 2018/04/04 06:00 PMCR- 2017/04/05 CRDT- 2017/04/16 06:00 PHST- 2017/03/21 00:00 [received] PHST- 2017/04/01 00:00 [accepted] PHST- 2017/04/16 06:00 [pubmed] PHST- 2018/04/04 06:00 [medline] PHST- 2017/04/16 06:00 [entrez] PHST- 2017/04/05 00:00 [pmc-release] AID - S2213-2317(17)30206-9 [pii] AID - 10.1016/j.redox.2017.04.001 [doi] PST - ppublish SO - Redox Biol. 2017 Aug;12:712-718. doi: 10.1016/j.redox.2017.04.001. Epub 2017 Apr 5.