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Proteins as Possible Targets for Cytotoxic trans ‐Platinum(II) Complexes with Aliphatic Amine Ligands: Further Exceptions to the DNA Paradigm
Author(s) -
Cubo Leticia,
Groessl Michael,
Dyson Paul J.,
Quiroga Adoración G.,
NavarroRanninger Carmen,
Casini Angela
Publication year - 2010
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201000104
Subject(s) - chemistry , oligonucleotide , peptide , adduct , amine gas treating , stereochemistry , cisplatin , dna , reactivity (psychology) , combinatorial chemistry , biochemistry , organic chemistry , biology , medicine , alternative medicine , chemotherapy , pathology , genetics
The reactivity of three cytotoxic trans ‐Pt II complexes bearing aliphatic amine ligands, with transferrin and single‐stranded oligonucleotides as DNA models, was investigated by ESI‐MS and the results obtained are discussed in comparison with cisplatin. Tandem MS studies provided additional information on the preferential Pt binding sites. To determine whether trans ‐Pt II complexes can migrate from a peptide to an oligonucleotide, transfer experiments were also performed using ESI‐MS, and competitive binding of the trans ‐Pt II complexes toward a model peptide and different oligonucleotides was also investigated. Significant differences in the reactivity of the trans complexes with respect to cisplatin were observed. In general, adduct formation with the selected peptide is favored for the trans compounds, whereas cisplatin shows a preference for oligonucleotides, especially if adjacent G–G residues are present. The results are discussed in relation to the possible mechanism of action of the trans ‐Pt II complexes.