Identification of creatine kinase and alpha-1 antitrypsin as protein targets of alkylation by sulfur mustard.
2D-thiol-DIGE
CEES
alkylating agents
high-resolution mass spectrometry
thiol groups
Journal
Drug testing and analysis
ISSN: 1942-7611
Titre abrégé: Drug Test Anal
Pays: England
ID NLM: 101483449
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
21
07
2020
revised:
16
08
2020
accepted:
18
08
2020
pubmed:
28
8
2020
medline:
25
2
2023
entrez:
28
8
2020
Statut:
ppublish
Résumé
Sulfur mustard (SM) is a toxic chemical warfare agent deployed in several conflicts within the last 100 years and still represents a threat in terroristic attacks and warfare. SM research focuses on understanding the pathophysiology of SM and identifying novel biomarkers of exposure. SM is known to alkylate nucleophilic moieties of endogenous proteins, for example, free thiol groups of cysteine residues. The two-dimensional-thiol-differences in gel electrophoresis (2D-thiol-DIGE) technique is an initial proteomics approach to detect proteins with free cysteine residues. These amino acids are selectively labeled with infrared-maleimide dyes visualized after GE. Cysteine residues derivatized by alkylating agents are no longer accessible for the maleimide-thiol coupling resulting in the loss of the fluorescent signal of the corresponding protein. To prove the applicability of 2D-thiol-DIGE, this technology was exemplarily applied to neat human serum albumin treated with SM, to lysates from human cell culture exposed to SM as well as to human plasma exposed to CEES (chloroethyl ethyl sulfide, an SM analogue). Exemplarily, the most prominent proteins modified by SM were identified by matrix-assisted laser desorption/ionization time-of-flight (tandem) mass spectrometry, MALDI-TOF MS(/MS), as creatine kinase (CK) from human cells and as alpha-1 antitrypsin (A1AT) from plasma samples. Peptides containing the residue Cys
Substances chimiques
Chemical Warfare Agents
0
alpha 1-Antitrypsin
0
Creatine Kinase
EC 2.7.3.2
Mustard Gas
T8KEC9FH9P
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
268-282Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : Research Training Group GRK 2338
Informations de copyright
© 2020 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.
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