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Determination of hexahydrophthalic anhydride adducts to human serum albumin

In English

Författare

Summary, in English

Hexahydrophthalic anhydride (HHPA) is a highly sensitizing industrial chemical that is known to covalently bind to endogenous proteins. The aim of this study was to determine the binding sites of HHPA to human serum albumin (HSA). Conjugates between HSA and HHPA, at two different molar ratios, were synthesized under physiological conditions. The conjugates were digested with trypsin and Pronase E to obtain specific peptides and amino acids, which were separated by liquid chromatography (LC). Fractions containing modified peptides were detected through quantification of hydrolysable HHPA using LC coupled to a triple quadrupole mass spectrometer with electrospray ionization. Modified residues in albumin were identified by sequence analyses using nanoelectrospray quadrupole time-of-flight mass spectrometry. A total of 36 HHPA adducts were found in the HSA - HHPA conjugate with 10 times molar excess of added HHPA. In the conjugate with a molar ratio of 1: 0.1 of added HHPA, seven HHPA adducts were found bound to Lys(137) (domain IB), Lys(190), Lys(199) and Lys(212) (domain IIA), Lys(351) (domain IIB), and Lys(432) and Lys(436) (domain IIIA). Moreover, several of these adducted albumin peptides were detected in nasal lavage fluid from one volunteer exposed to HHPA. The binding sites of HHPA to HSA have been determined, thus identifying potential allergenic chemical structures. This knowledge generates the possibility of developing methods for the biological monitoring of HHPA exposure by analysing tryptic peptides including these binding sites.

Publiceringsår

2003

Språk

Engelska

Sidor

343-359

Publikation/Tidskrift/Serie

Biomarkers

Volym

8

Issue

5

Dokumenttyp

Artikel i tidskrift

Förlag

Taylor & Francis

Ämne

  • Environmental Health and Occupational Health

Nyckelord

  • liquid chromatography/mass spectrometry
  • organic acid anhydrides
  • protein adducts

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1366-5804