PMID- 30468304
OWN - NLM
STAT- MEDLINE
DCOM- 20190813
LR  - 20190813
IS  - 1942-7611 (Electronic)
IS  - 1942-7603 (Linking)
VI  - 11
IP  - 5
DP  - 2019 May
TI  - Methionine(329) in human serum albumin: A novel target for alkylation by sulfur 
      mustard.
PG  - 659-668
LID - 10.1002/dta.2548 [doi]
AB  - Exposure to the vesicant sulfur mustard (SM) may lead to erythema and blistering. 
      Toxicity of SM is hypothesized due to the alkylation of DNA bases and 
      nucleophilic amino acid side chains in proteins (adducts) by forming the 
      hydroxyethylthioethyl (HETE) moiety. Despite its prohibition by the chemical 
      weapons convention, SM still represents a serious threat to military personnel 
      and civilians. Therefore, development and improvement of forensic analytical 
      methods for the verification of SM exposure is of high interest. Protein adducts 
      have been shown to be highly suitable and beneficial biomarkers of poisoning. 
      Herein we present methionine(329) in human serum albumin (HSA) as a novel target 
      of SM forming a HETE-methionyl sulfonium ion. The alkylated tetrapeptide 
      LeuGlyMet(329) (-HETE)Phe, LGM(-HETE)F, was detected after pepsin-mediated 
      proteolysis and subsequent analysis by microbore liquid 
      chromatography-electrospray ionization-high-resolution tandem-mass spectrometry. 
      Compound identity was confirmed by a synthetic reference. Proteolysis conditions 
      for HSA were optimized towards maximum yield of LGM(-HETE)F and its limit of 
      identification (32.3 nM SM in serum) was similar to those of the established 
      HSA-derived biomarkers HETE-CysPro and HETE-CysProPhe (15.6 nM SM in serum). 
      Stability of the alkylated Met(329) in vitro and in vivo was limited to 5 days 
      making this modification a beneficial short-time biomarker. Furthermore, it was 
      found that the HETE-methionyl sulfonium ion can transfer its HETE moiety to the 
      side chain of cysteine and glutamic acid as well as to the N-terminus of peptides 
      and proteins in vitro thus revealing novel insights into the molecular toxicity 
      of SM.
CI  - (c) 2018 John Wiley & Sons, Ltd.
FAU - Siegert, Markus
AU  - Siegert M
AUID- ORCID: 0000-0003-1760-7733
AD  - Department of Chemistry, Humboldt-Universitat zu Berlin, Brook-Taylor-Strasse 2, 
      12489, Berlin, Germany.
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937, 
      Munich, Germany.
FAU - Gandor, Felix
AU  - Gandor F
AD  - Department of Chemistry, Humboldt-Universitat zu Berlin, Brook-Taylor-Strasse 2, 
      12489, Berlin, Germany.
FAU - Kranawetvogl, Andreas
AU  - Kranawetvogl A
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937, 
      Munich, Germany.
FAU - Borner, Hans
AU  - Borner H
AD  - Department of Chemistry, Humboldt-Universitat zu Berlin, Brook-Taylor-Strasse 2, 
      12489, Berlin, Germany.
FAU - Thiermann, Horst
AU  - Thiermann H
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937, 
      Munich, Germany.
FAU - John, Harald
AU  - John H
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937, 
      Munich, Germany.
LA  - eng
PT  - Journal Article
DEP - 20190122
PL  - England
TA  - Drug Test Anal
JT  - Drug testing and analysis
JID - 101483449
RN  - 0 (Chemical Warfare Agents)
RN  - AE28F7PNPL (Methionine)
RN  - T8KEC9FH9P (Mustard Gas)
RN  - ZIF514RVZR (Serum Albumin, Human)
MH  - Alkylation/*drug effects
MH  - Chemical Warfare Agents/*toxicity
MH  - Humans
MH  - Methionine/*analysis
MH  - Mustard Gas/*toxicity
MH  - Serum Albumin, Human/*chemistry
MH  - Spectrometry, Mass, Electrospray Ionization
OTO - NOTNLM
OT  - albumin-adducts
OT  - alkylation
OT  - high-resolution mass spectrometry
OT  - methionyl sulfonium
OT  - sulfur mustard
EDAT- 2018/11/24 06:00
MHDA- 2019/08/14 06:00
CRDT- 2018/11/24 06:00
PHST- 2018/10/03 00:00 [received]
PHST- 2018/11/15 00:00 [revised]
PHST- 2018/11/16 00:00 [accepted]
PHST- 2018/11/24 06:00 [pubmed]
PHST- 2019/08/14 06:00 [medline]
PHST- 2018/11/24 06:00 [entrez]
AID - 10.1002/dta.2548 [doi]
PST - ppublish
SO  - Drug Test Anal. 2019 May;11(5):659-668. doi: 10.1002/dta.2548. Epub 2019 Jan 22.