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Determination of the toluene diisocyanate binding sites on human serum albumin by tandem mass spectrometry.

Authors
Hettick-JM; Siegel-PD
Source
Anal Biochem 2011 Jul; 414(2):232-238
NIOSHTIC No.
20038593
Abstract
Diisocyanates are highly reactive chemical compounds widely used in the manufacture of polyurethanes. Although diisocyanates have been identified as causative agents of allergic respiratory diseases, the specific mechanism by which these diseases occur is largely unknown. To better understand the chemical species produced when diisocyanates react with protein, tandem mass spectrometry was employed to unambiguously identify the binding sites of the industrially important isomers, 2,4- and 2,6-toluene diisocyanate on human serum albumin at varying diisocyanate:protein ratios. The 2,4- isomer results in approximately two-fold higher conjugation product ion abundances than does the 2,6- isomer, suggesting the 2,4- isomer has a higher reactivity towards albumin. Both isomers preferentially react with the N-terminal amine of the protein and the epsilon-NH2 of lysine. At a low (1:2) diisocyanate:protein ratio, five binding sites are identified, whereas at a high 40:1 ratio, near-stoichiometric conjugation is observed with a maximum of thirty-seven binding sites identified. Binding sites observed at the lowest conjugation ratios are conserved at higher binding ratios suggesting a subset of five to ten preferential binding sites on albumin. Diisocyanate-protein conjugation results in a variety of different reaction products, including intra- and inter-molecular crosslinking, diisocyanate selfpolymerization, and diisocyanate hydrolysis.
Keywords
Mass-spectrometry; Allergic-reactions; Allergies; Respiratory-system-disorders; Pulmonary-system-disorders; Lung-irritants; Lung-disorders; Respiratory-irritants; Protein-biochemistry; Author Keywords: Diisocyanate; Serum albumin; Tandem mass spectrometry
Contact
Justin M. Hettick, Ph.D., NIOSH/HELD/ACIB, 1095 Willowdale Rd., MS L4020, Morgantown, WV 26505
CODEN
ANBCA2
CAS No.
584-84-9
Publication Date
20110715
Document Type
Journal Article
Email Address
jhettick@cdc.gov
Fiscal Year
2011
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
0003-2697
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Analytical Biochemistry
State
WV
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