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Histidine Targeting Heterobimetallic Ruthenium(II)–Gold(I) Complexes

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Batchelor Lucinda K., Ortiz Daniel, Dyson Paul J.,
Project Modulation of the site specificity of binding of metal-based drugs to chromatin
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Original article (peer-reviewed)

Journal Inorganic Chemistry
Volume (Issue) 58(4)
Page(s) 2501 - 2513
Title of proceedings Inorganic Chemistry
DOI 10.1021/acs.inorgchem.8b03069

Open Access

Type of Open Access Publisher (Gold Open Access)


Inspired by the preferential, allosteric binding of RAPTA-T and auranofin to the nucleosome core particle , we describe the design and synthesis of a series of heterobimetallic ruthenium(II)−gold(I) complexes with varying spacer lengths ranging from four to eight polyethylene glycol units. Evaluation of their cytotoxicity reveals IC50 values in the low micromolar range against cisplatin sensitive and resistant human ovarian carcinoma (A2780, A2780cisR) and nontumoral human embryonic kidney (HEK293) cell lines. Binding studies monitored via mass spectrometry revealed an affinity for histidine residues on a fragment of the amyloid β-protein (residues 1−16, employed as a model system), which is in accordance with the binding sites of parent drugs, RAPTA-C and auranofin, to the nucleosome core particle.