Abstract
Protein covalent adducts formed upon exposure to reactive (mainly electrophilic) chemicals may lead to the development of a wide range of deleterious health outcomes. Therefore, the identification of protein covalent adducts constitutes a huge opportunity for a better understanding of events underlying diseases and for the development of biomarkers which may constitute effective tools for disease diagnosis/prognosis, for the application of personalized medicine approaches and for accurately assessing human exposure to chemical toxicants. The currently available mass spectrometry (MS)-based methodologies, are clearly the most suitable for the analysis of protein covalent modifications, providing accuracy, sensitivity, unbiased identification of the modified residue and conjugates along with quantitative information. However, despite the huge technological advances in MS instrumentation and bioinformatics tools, the identification of low abundant protein covalent adducts is still challenging. This review is aimed at summarizing the MS-based methodologies currently used for the identification of protein covalent adducts and the strategies developed to overcome the analytical challenges, involving not only sample pre-treatment procedures but also distinct MS and data analysis approaches.
Highlights
Protein covalent adducts are formed upon exposure to reactive chemical agents from internal or external exposures
Studies focused on the identification of protein covalent adducts are often classified as: 1) targeted, when focused on identifying covalent adducts formed upon exposure to a specific chemical agent; or 2) untargeted, aimed at comprehensively characterizing the totality of covalent conjugates bound to a specific nucleophilic residue of a protein
One of the first examples of this strategy involved the use of biotin affinity probes to capture and, thereby, enrich protein and peptide adducts formed with lipid-derived electrophiles (LDEs) containing an aldehyde group [13,14,15]
Summary
Protein covalent adducts are formed upon exposure to reactive chemical agents (mainly electrophiles) from internal or external exposures. One of the first examples of this strategy involved the use of biotin affinity probes to capture and, thereby, enrich protein and peptide adducts formed with lipid-derived electrophiles (LDEs) containing an aldehyde group [13,14,15]. This strategy was recently applied for the identification of acrolein protein adducts in human lung epithelial cells [16]. While the in vivo application of this technically relatively simple method has not yet been provided, it is potentially a methodology for application in the label-free analysis of protein covalent adducts
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
