Batchelor LK De Falco L von Erlach T Sharma D Adhireksan Z Roethlisberger U Davey CA Dyson PJ 2019 Targeting defined histone protein sites in chromatin is an emerging therapeutic approach that can potentially be enhanced by allosteric effects within the nucleosome. Here we characterized a novel hetero-bimetallic compound with a design based on a nucleosomal allostery effect observed earlier for two unrelated drugs-the RuII antimetastasis/antitumor RAPTA-T and the AuI anti-arthritic auranofin. The RuII moiety binds specifically to two H2A glutamate residues on the nucleosome acidic patch, allosterically triggering a cascade of structural changes that promote binding of the AuI moiety to selective histidine residues on H3, resulting in cross-linking sites that are over 35 Å distant. By tethering the H2A-H2B dimers to the H3-H4 tetramer, the hetero-bimetallic compound significantly increases stability of the nucleosome, illustrating its utility as a site-selective cross-linking agent. https://sonar.ch/global/documents/214607 eng info:eu-repo/semantics/altIdentifier/doi/10.1002/anie.201906423 info:eu-repo/semantics/altIdentifier/pmid/31478581 Angewandte Chemie (International ed. in English). - 2019 allostery bioinorganic chemistry macromolecular crystallography molecular dynamics simulations nucleosome structure Allosteric Site Cross-Linking Reagents Models, Molecular Molecular Structure Nucleosomes Crosslinking Allosteric Sites on the Nucleosome. http://purl.org/coar/resource_type/c_6501