Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of titanium oxide-enriched peptides for detection of aged organophosphorus adducts on human butyrylcholinesterase

Wei Jiang, Ekaterina A. Murashko, Yaroslav A. Dubrovskii, Ekaterina P. Podolskaya, Vladimir N. Babakov, John Mikler, Florian Nachon, Patrick Masson, Lawrence M. Schopfer, Oksana Lockridge

Research output

16 Citations (Scopus)

Abstract

Exposure to nerve agents or organophosphorus (OP) pesticides can have life-threatening effects. Human plasma butyrylcholinesterase (BChE) inactivates these poisons by binding them to Ser198. After hours or days, these OP adducts acquire a negative charge by dealkylation in a process called aging. Our goal was to develop a method for enriching the aged adduct to facilitate detection of exposure. Human BChE inhibited by OP toxicants was incubated for 4 days to 6 years. Peptides produced by digestion with pepsin were enriched by binding to titanium oxide (TiO2) and analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. It was found that with two exceptions, all aged OP adducts in peptide FGES 198AGAAS were enriched by binding to Titansphere tips. Cresyl saligenin phosphate yielded two types of aged adduct, cresylphosphate and phosphate, but only the phosphate adduct bound to Titansphere. The nerve agent VR yielded no aged adduct, supporting crystal structure findings that the VR adduct on BChE does not age. The irreversible nature of aged OP adducts was demonstrated by the finding that after 6 years at room temperature in sterile pH 7.0 buffer, the adducts were still detectable. It was concluded that TiO 2 microcolumns can be used to enrich aged OP-modified BChE peptide.

Original languageEnglish
Pages (from-to)132-141
Number of pages10
JournalAnalytical Biochemistry
Volume439
Issue number2
DOIs
Publication statusPublished - 1 Jan 2013

Fingerprint

Butyrylcholinesterase
Ionization
Mass spectrometry
Desorption
Mass Spectrometry
Lasers
Peptides
Phosphates
Dealkylation
Plasma (human)
Poisons
Pepsin A
Pesticides
Digestion
Buffers
Aging of materials
Crystal structure
Temperature
titanium dioxide

Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Jiang, Wei ; Murashko, Ekaterina A. ; Dubrovskii, Yaroslav A. ; Podolskaya, Ekaterina P. ; Babakov, Vladimir N. ; Mikler, John ; Nachon, Florian ; Masson, Patrick ; Schopfer, Lawrence M. ; Lockridge, Oksana. / Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of titanium oxide-enriched peptides for detection of aged organophosphorus adducts on human butyrylcholinesterase. In: Analytical Biochemistry. 2013 ; Vol. 439, No. 2. pp. 132-141.
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abstract = "Exposure to nerve agents or organophosphorus (OP) pesticides can have life-threatening effects. Human plasma butyrylcholinesterase (BChE) inactivates these poisons by binding them to Ser198. After hours or days, these OP adducts acquire a negative charge by dealkylation in a process called aging. Our goal was to develop a method for enriching the aged adduct to facilitate detection of exposure. Human BChE inhibited by OP toxicants was incubated for 4 days to 6 years. Peptides produced by digestion with pepsin were enriched by binding to titanium oxide (TiO2) and analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. It was found that with two exceptions, all aged OP adducts in peptide FGES 198AGAAS were enriched by binding to Titansphere tips. Cresyl saligenin phosphate yielded two types of aged adduct, cresylphosphate and phosphate, but only the phosphate adduct bound to Titansphere. The nerve agent VR yielded no aged adduct, supporting crystal structure findings that the VR adduct on BChE does not age. The irreversible nature of aged OP adducts was demonstrated by the finding that after 6 years at room temperature in sterile pH 7.0 buffer, the adducts were still detectable. It was concluded that TiO 2 microcolumns can be used to enrich aged OP-modified BChE peptide.",
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author = "Wei Jiang and Murashko, {Ekaterina A.} and Dubrovskii, {Yaroslav A.} and Podolskaya, {Ekaterina P.} and Babakov, {Vladimir N.} and John Mikler and Florian Nachon and Patrick Masson and Schopfer, {Lawrence M.} and Oksana Lockridge",
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Jiang, W, Murashko, EA, Dubrovskii, YA, Podolskaya, EP, Babakov, VN, Mikler, J, Nachon, F, Masson, P, Schopfer, LM & Lockridge, O 2013, 'Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of titanium oxide-enriched peptides for detection of aged organophosphorus adducts on human butyrylcholinesterase', Analytical Biochemistry, vol. 439, no. 2, pp. 132-141. https://doi.org/10.1016/j.ab.2013.04.018

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of titanium oxide-enriched peptides for detection of aged organophosphorus adducts on human butyrylcholinesterase. / Jiang, Wei; Murashko, Ekaterina A.; Dubrovskii, Yaroslav A.; Podolskaya, Ekaterina P.; Babakov, Vladimir N.; Mikler, John; Nachon, Florian; Masson, Patrick; Schopfer, Lawrence M.; Lockridge, Oksana.

In: Analytical Biochemistry, Vol. 439, No. 2, 01.01.2013, p. 132-141.

Research output

TY - JOUR

T1 - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of titanium oxide-enriched peptides for detection of aged organophosphorus adducts on human butyrylcholinesterase

AU - Jiang, Wei

AU - Murashko, Ekaterina A.

AU - Dubrovskii, Yaroslav A.

AU - Podolskaya, Ekaterina P.

AU - Babakov, Vladimir N.

AU - Mikler, John

AU - Nachon, Florian

AU - Masson, Patrick

AU - Schopfer, Lawrence M.

AU - Lockridge, Oksana

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Exposure to nerve agents or organophosphorus (OP) pesticides can have life-threatening effects. Human plasma butyrylcholinesterase (BChE) inactivates these poisons by binding them to Ser198. After hours or days, these OP adducts acquire a negative charge by dealkylation in a process called aging. Our goal was to develop a method for enriching the aged adduct to facilitate detection of exposure. Human BChE inhibited by OP toxicants was incubated for 4 days to 6 years. Peptides produced by digestion with pepsin were enriched by binding to titanium oxide (TiO2) and analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. It was found that with two exceptions, all aged OP adducts in peptide FGES 198AGAAS were enriched by binding to Titansphere tips. Cresyl saligenin phosphate yielded two types of aged adduct, cresylphosphate and phosphate, but only the phosphate adduct bound to Titansphere. The nerve agent VR yielded no aged adduct, supporting crystal structure findings that the VR adduct on BChE does not age. The irreversible nature of aged OP adducts was demonstrated by the finding that after 6 years at room temperature in sterile pH 7.0 buffer, the adducts were still detectable. It was concluded that TiO 2 microcolumns can be used to enrich aged OP-modified BChE peptide.

AB - Exposure to nerve agents or organophosphorus (OP) pesticides can have life-threatening effects. Human plasma butyrylcholinesterase (BChE) inactivates these poisons by binding them to Ser198. After hours or days, these OP adducts acquire a negative charge by dealkylation in a process called aging. Our goal was to develop a method for enriching the aged adduct to facilitate detection of exposure. Human BChE inhibited by OP toxicants was incubated for 4 days to 6 years. Peptides produced by digestion with pepsin were enriched by binding to titanium oxide (TiO2) and analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. It was found that with two exceptions, all aged OP adducts in peptide FGES 198AGAAS were enriched by binding to Titansphere tips. Cresyl saligenin phosphate yielded two types of aged adduct, cresylphosphate and phosphate, but only the phosphate adduct bound to Titansphere. The nerve agent VR yielded no aged adduct, supporting crystal structure findings that the VR adduct on BChE does not age. The irreversible nature of aged OP adducts was demonstrated by the finding that after 6 years at room temperature in sterile pH 7.0 buffer, the adducts were still detectable. It was concluded that TiO 2 microcolumns can be used to enrich aged OP-modified BChE peptide.

KW - Aged organophosphorus adducts

KW - Human butyrylcholinesterase

KW - Mass spectrometry

KW - Titanium oxide

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