Determination of hexahydrophthalic anhydride adducts to human serum albumin

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Kåredal, MonicaLund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine (author)

Determination of hexahydrophthalic anhydride adducts to human serum albumin

Article/chapterEnglish2003

Publisher, publication year, extent ...

2008-10-04
Informa UK Limited,2003

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LIBRIS-ID:oai:lup.lub.lu.se:a6f54c41-6e1d-4c4e-b35a-2caead9efd13
https://lup.lub.lu.se/record/296574URI
https://doi.org/10.1080/13547500310001607836DOI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

Notes

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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Hälsovetenskap Arbetsmedicin och miljömedicin hsv//swe
MEDICAL AND HEALTH SCIENCES Health Sciences Occupational Health and Environmental Health hsv//eng
liquid chromatography/mass spectrometry
organic acid anhydrides
protein adducts

Added entries (persons, corporate bodies, meetings, titles ...)

Lindh, ChristianLund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)ymed-cli (author)
Jönsson, Bo ALund University,Lunds universitet,Avdelningen för arbets- och miljömedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Occupational and Environmental Medicine, Lund University,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)ymed-bjo (author)
Avdelningen för arbets- och miljömedicinInstitutionen för laboratoriemedicin (creator_code:org_t)

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In:Biomarkers: Informa UK Limited8:5, s. 343-3591366-58041354-750X

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By the author/editor: Kåredal, Monica; Lindh, Christian; Jönsson, Bo A

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Health Sciences; and Occupational Hea ...

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By the university: Lund University

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