Table 3.
Overview of protein adductome studies using LC-MS.
| Sample | MS type a | Scan mode b |
Fragmentation method |
Features of untargeted detection |
Adducts identified | Year | Reference |
|---|---|---|---|---|---|---|---|
| Kidney tissue from male Eker rats | Ion trap | DDA-MS2 | Trap-type CID | Peptide sequencing | 2-(glutathion-S-yl)-1,4-benzoquinone-derived protein adducts | 2009 | [162] |
| Rabbit muscle, bacterium (E. coli) | LIT-Orbitrap | DDA-MS2 | Trap-type CID | Peptide sequencing | Mercury-derived protein adducts | 2011 | [163] |
| Human serum albumin (HSA) | QqQ | FS-SRM | Beam-type CID | Specific product ions of HSA-cysteine-34 (Cys34) | Protein adducts associated with environmental exposure | 2012 | [164] |
| Human plasma | LIT-Orbitrap | DDA-MS2 | Trap-type CID | Specific product ions of HSA-Cys34 | HSA-Cys34 adducts derived from oxidation and cysteinylation | 2014 | [165] |
| Red blood cells (RBCs) from smokers and nonsmokers | QTRAP | FS-SRM | Beam-type CID | Specific product ions of fluorescein thiohydantoin (FTH) derivatives | Hb N-terminal valine (Val) adducts | 2014 | [141] |
| Hemoglobin (Hb) peptide, human blood and plasma | Q-Orbitrap | DIA | HCD | Specific product ions of HSA-Cys34 and Hb cysteine-93 | HSA-Cys34 adducts associated with oxidative stress | 2015 | [147] |
| RBCs (human, bovine, rabbit, guinea pig and mice) | QTRAP | FS-SRM | Beam-type CID | Specific product ions of FTH derivatives | Ethyl vinyl ketone-derived Hb N-terminal Val adducts | 2015 | [166] |
| Human plasma | LIT-Orbitrap | DDA-MS2 | Trap-type CID | Specific product ions of HSA-Cys34 | HSA-Cys34 adducts associated with cigarette smoking | 2016 | [139] |
| Human and mice serum | QqQ | FS-SRM | Beam-type CID | Diagnostic product ion of Lys and histidine (His) | LPO-derived protein adducts | 2017 | [155] |
| RBCs from school-age children | Q-Orbitrap | DIA | HCD | Specific product ions of FTH derivatives | Genotoxic compounds-derived Hb N-terminal Val adducts | 2017 | [167] |
| Human plasma | LIT-Orbitrap | DDA-MS2 | Trap-type CID | Specific product ions of HSA-Cys34 | HSA-Cys34 adducts associated with solid fuel | 2017 | [132] |
| Human plasma | QqQ | FS-SRM | Beam-type CID | NL of b5 fragment in T3 peptide | HSA adducts associated with environmental exposure | 2017 | [144] |
| Human serum | LIT-Orbitrap | DDA-MS2 | Trap-type CID | Specific product ions of HSA-Cys34 | Benzene oxide- and diolepoxide-derived protein adducts | 2018 | [168] |
| Human serum | LIT-Orbitrap | DDA-MS2 | Trap-type CID | Specific product ions of HSA-Cys34 | HSA-Cys34 adducts associated with chronic obstructive pulmonary disease and ischemic heart disease | 2018 | [169] |
| Human RBCs | Q-Orbitrap | DIA | HCD | Specific product ions of FTH derivatives | 4-Quinone methide- and 4-hydroxybenzaldehyde-derived Hb N-terminal Val adducts | 2018 | [170] |
| THLE-2 and Hep G2 cells | Q-TOF | DDA-MS2 | Beam-type CID | Methionine (Met) oxidation, specific mass increments corresponding to glycidamide incorporation at Lys, Cys, His, serine (Ser), arginine (Arg) | Glycidamide-derived protein adducts | 2019 | [157] |
| Human serum | LIT-Orbitrap | DDA-MS2 | Trap-type CID | Specific product ions of HSA-Cys34 | HSA-Cys34 adducts associated with colorectal cancer | 2019 | [171] |
| Newborn dried blood spots | LIT-Orbitrap | DDA-MS2 | Trap-type CID | Specific product ions of HSA-Cys34 | HSA-Cys34 adducts associated with smoking | 2019 | [138] |
| Human RBCs | QqQ | FS-SRM | Beam-type CID | Diagnostic fragment ion m/z 110 for His adduct and m/z 84 for Lys adduct | 2-Alkenal-derived His and Lys adducts | 2019 | [156] |
| Human serum | Q-TOF, LTQ-Orbitrap, Q-Orbitrap | Full scan, DDA-MS2, parallel reaction monitoring (PRM) | Trap-type CID, HCD | Peptide sequencing; bottom-up trypsin-PRM methods | Catechol estrogens (CEs)-derived HSA adducts | 2019 | [158] |
| THP-1 cells, human pulmonary macrophages | Q-Orbitrap | DDA-MS2 | HCD | Cys carbamidomethylation, Met oxidation, N-terminal glutamine deamidation, and Lys aSA-triazole-hexanoic acid modification | Oxysterols-derived protein adducts | 2020 | [172] |
| Human plasma | LIT-Orbitrap | DDA-MS2 | Trap-type CID | Specific product ions of HSA-Cys34 | HSA-Cys34 adducts associated with lung cancer | 2020 | [173] |
| Human plasma and RBCs | Q-Orbitrap | DDA-MS2 | HCD | Met oxidation, Cys carbamidomethylation, and specific mass increments corresponding to hapten incorporation at Cys, His, Lys, Arg, Ser, tyrosine (Tyr), threonine, and N-terminus of peptides | Protein adducts associated with skin allergens | 2020 | [174] |
| Newborn neonatal blood spots | LIT-Orbitrap | DDA-MS2 | Trap-type CID | Specific product ions of HSA-Cys34 | HSA-Cys34 adducts associated with childhood acute lymphoblastic leukemia and acute myeloid leukemia (AML) | 2020 | [175] |
| Giardia Lamblia (strain WB and GS/M) | Q-TOF | DDA-MS2 | Beam-type CID | Peptide sequencing; click-chemistry adduction of metronidazole alkyne-tagged proteins | 5-nitroimidazoles-derived protein adducts | 2020 | [160] |
| Human plasma from smokers and nonsmokers | LIT-Orbitrap | DDA-MS2 | Trap-type CID | Specific product ions of HSA-Cys34 and lysine-525 (Lys525) | HSA-Cys34 and HSA-Lys525 adducts | 2021 | [148] |
| Human plasma and RBCs | Q-TOF, LTQ-Orbitrap, Q-Orbitrap | Full scan, DDA-MS2, PRM | Trap-type CID, HCD | Peptide sequencing; bottom-up trypsin-PRM methods | CEs-derived Hb and HSA adducts | 2021 | [159] |
| Human plasma | LIT-Orbitrap | DDA-MS2 | Trap-type CID | Specific product ions of HSA-Cys34 and Lys525 | HSA-Cys34 and HSA-Lys525 adducts associated with diesel engine exhaust | 2022 | [176] |
| RBCs from schoolchildren, human adults and rodents | Q-Orbitrap | DDA-MS2 | HCD | Specific product ions of FTH derivatives | Hydroxypropanoic acid-Val adduct in Hb | 2022 | [151] |
| Human plasma and serum | LIT-Orbitrap | DDA-MS2 | Trap-type CID | Specific product ions of HSA-Cys34 | HSA-Cys34 adducts associated with AML | 2023 | [146] |
| Human serum | Q-LIT-Orbitrap | DIA | HCD | Specific mass increment (e.g., oxidation and acetylation) on Cys34 and other residues, including Lys, His, Tyr, Ser, Met, and Arg | HSA adducts associated with air pollution | 2023 | [149] |
| Human serum | LIT-Orbitrap | DDA-MS2 | Trap-type CID | Specific product ions of HSA-Cys34 | HSA-Cys34 and HSA-Lys525 adducts associated with non-Hodgkin lymphoma | 2023 | [177] |
| Human RBCs | Q-Orbitrap | PRM, DDA-MS2 | HCD | Specific product ions of FTH derivatives; bottom-up MS-based proteomics | Hb N-terminal Val adducts associated with allergens and electrophiles | 2023 | [153] |
| Human brain tumor tissue | Q-Orbitrap | DDA-MS2 | HCD | Peptide sequencing | Protein adducts associated with pesticides exposure | 2023 | [178] |
| Human coronary artery smooth muscle cells | TIMS-TOF | DDA-MS2, parallel accumulat ion-serial fragmenta tion combined with DIA (DIA-PASEF) | HCD | Peptide sequencing; click-chemistry adduction of alkyne-tagged proteins | Dimethylfumarate- and monomethylfumarate-derived protein adducts | 2023 | [161] |
| Human serum | Q-Orbitrap | DDA-MS2 | HCD | Specific product ions of HSA-Cys34 | HSA adducts associated with water-soluble organic molecules in inhaled PM2.5 | 2024 | [145] |
| Plasma from preterm and full-term infants | LTQ-Orbitrap | Full scan | NA | Peptide sequencing with manual inspection using Xcalibur™ software | HSA-Cys34 adducts linked to oxidative stress caused by bronchopulmonary dysplasia | 2024 | [179] |
a
LRMS includes QqQ, ion trap and QTRAP instruments while HRMS includes LIT-Orbitrap, Q-Orbitrap, Q-LIT-orbitrap, Q-TOF and TIMS-TOF instruments.
b
Beam-type CID and HCD collisions in quadrupole or multipole cells typically produce numerous fragments, whereas trap-type CID collisions in ion traps yield fewer fragments.
NA: not available.