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Following incubation periods of 3\u2005h for cisplatin\u2013blood serum mixtures and subsequent trypsin digestion, MS\u2013MS spectra were recorded for individual peptides that had been separated by SCX and RP liquid chromatography. Matching of the MS\u2013MS spectra to theoretical sequences that were generated for human proteins in the SWISS\u2010PROT database led to the identification of specific binding sites in human serum albumin (HSA), serotransferrin (Trfe) and other abundant serum proteins (A2mg, A1at, Apoa1, Apoa2). The cisplatin coordination sites in HSA and Trfe were confirmed by independent MudPIT studies on cisplatin reaction mixtures with the individual proteins. A total of five specific binding sites were identified for HSA, including the cysteine residue C34, two methionine sites (M329, M548) and the tyrosine and aspartate O\u2010donor sites Y150 (or Y148) and D375 (or E376). Methionine\u2010256 was established as a cisplatin coordination site for Trfe in addition to the O\u2010donor sites E265, Y314, E385 and T457. Inspection of the protein structures indicates that the preferred residues belong either to peripheral <jats:italic>\u03b1\u2005<\/jats:italic>helices or to flexible loops within the protein\u2010binding pockets. O\u2010donor residues dominate as cisplatin binding sites for other abundant serum proteins.<\/jats:p>","DOI":"10.1002\/cmdc.200800151","type":"journal-article","created":{"date-parts":[[2008,10,15]],"date-time":"2008-10-15T02:05:37Z","timestamp":1224036337000},"page":"1696-1707","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Characterisation of Cisplatin Binding Sites in Human Serum Proteins Using Hyphenated Multidimensional Liquid Chromatography and ESI Tandem Mass Spectrometry"],"prefix":"10.1002","volume":"3","author":[{"given":"Joanna","family":"Will","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk\u2005A.","family":"Wolters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William\u2005S.","family":"Sheldrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,11,6]]},"reference":[{"key":"e_1_2_6_1_2","first-page":"1310","volume":"33","author":"DeConti R. 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