{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:05:09Z","timestamp":1789376709505,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,5,4]],"date-time":"2012-05-04T00:00:00Z","timestamp":1336089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2012,6,30]]},"abstract":"<jats:sec>\n                    <jats:title>RATIONALE<\/jats:title>\n                    <jats:p>\n                      <jats:italic>para<\/jats:italic>\n                      \u2010Phenylenediamine (PPD) is a potent and well\u2010known allergen, which is commonly used in hair or fur dyes and can cause severe allergic contact dermatitis. In this work, the skin\u2010sensitizing potential of PPD with respect to the conjugation of proteins was evaluated using an approach without animal testing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Electrochemistry (EC) coupled offline to liquid chromatography (LC) and electrospray ionization mass spectrometry (ESI\u2010MS) was employed to convert the pre\u2010hapten PPD into its reactive hapten analogs. A previous study had already shown that this purely instrumental method is suitable for accelerating and simulating the various oxidation processes, which PPD may undergo, and that the emerging products are prone to react with soft thiol groups of small nucleophiles like glutathione and cysteine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      This investigation was extended by successfully demonstrating adduct formation between EC\u2010generated PPD oxidation products and the three proteins\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010lactoglobulin A (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010LGA), human serum albumin and human hemoglobin. A tryptic digest of modified\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010LGA provided evidence for irreversible protein binding of monomeric PPD, a PPD dimer and the PPD trimer known as Bandrowski's Base. It was shown that the main oxidation product\n                      <jats:italic>p<\/jats:italic>\n                      \u2010phenylene quinone diimine, and the reactive oligomerized species, primarily attack the free thiol function of proteins rather than other nucleophilic amino acid residues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>\n                      The pre\u2010hapten PPD was efficiently activated upon EC oxidation and the resulting species were further reacted with different proteins leading to diverse hapten\u2010protein complexes. Thereby, problems related to the complex matrix present in conventional\n                      <jats:italic>in vitro<\/jats:italic>\n                      or\n                      <jats:italic>in vivo<\/jats:italic>\n                      methods could effectively be avoided. Copyright \u00a9 2012 John Wiley &amp; Sons, Ltd.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.6247","type":"journal-article","created":{"date-parts":[[2012,5,7]],"date-time":"2012-05-07T00:57:22Z","timestamp":1336352242000},"page":"1415-1425","source":"Crossref","is-referenced-by-count":20,"title":["Electrochemistry\/liquid chromatography\/mass spectrometry to demonstrate irreversible binding of the skin allergen\n                    <i>p<\/i>\n                    \u2010phenylenediamine to proteins"],"prefix":"10.1002","volume":"26","author":[{"given":"Sandra","family":"Jahn","sequence":"first","affiliation":[{"name":"University of M\u00fcnster Institute of Inorganic and Analytical Chemistry and NRW Graduate School of Chemistry  Corrensstr. 30 48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Faber","sequence":"additional","affiliation":[{"name":"University of M\u00fcnster Institute of Inorganic and Analytical Chemistry and NRW Graduate School of Chemistry  Corrensstr. 30 48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raniero","family":"Zazzeroni","sequence":"additional","affiliation":[{"name":"Unilever UK SEAC  Colworth Science Park Sharnbrook MK44 1LQ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Karst","sequence":"additional","affiliation":[{"name":"University of M\u00fcnster Institute of Inorganic and Analytical Chemistry and NRW Graduate School of Chemistry  Corrensstr. 30 48149 M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,5,4]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.61.5.643"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.64.4.625"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2230.2003.01239.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0625.2000.009003165.x"},{"key":"e_1_2_6_6_1","volume-title":"Allergic Contact Dermatitis: Chemical and Metabolic Mechanisms","author":"Smith C. 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