Proof of Phosphate Diester Binding Ability of Cytotoxic DNA-Binding Complexes
| Autor: | Anja Stammler, Jasmin Simon, Hartmut Bögge, Jan Oldengott, Thorsten Glaser |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
010405 organic chemistry
Stereochemistry Metal ions in aqueous solution digestive oral and skin physiology Antineoplastic Agents Esters DNA 010402 general chemistry Phosphate 01 natural sciences Phosphates 0104 chemical sciences Inorganic Chemistry Binding ability chemistry.chemical_compound chemistry Coordination Complexes Nickel Cell Line Tumor Humans Cytotoxic T cell Physical and Theoretical Chemistry Copper |
| Popis: | We have rationally designed a family of dinuclear transition-metal complexes to bind two neighboring phosphate diester groups of DNA. The two metal ions are positioned at the distance of two neighboring phosphate diesters in DNA of 6-7 A by a 1,8-naphthalenediol backbone. Two sterically demanding dipicolylamine pendant arms in the 2 and 7 positions stabilize coordination of the metal ions and prevent coordination to the less exposed nucleobases of DNA. Although the dinuclear NiII2 and CuII2 bind to DNA, inhibit DNA synthesis, and preferentially kill human cancer cells over fast proliferating human stem cells, the DNA binding mode was elusive. Here, we prove the principle phosphate diester binding ability of this family of dinuclear complexes by a new dinuclear NiII2 complex with dibenzimidazolamine pendant arms. The distance of the oxygen atoms of the coordinated phosphate diesters of 6.5 A confirms the initial design and binding ability to two neighboring phosphate diesters of the DNA backbone. Moreover, the facile exchange of coordinated acetates by phosphate diesters indicates a preferential binding to phosphate diesters. |
| Databáze: | OpenAIRE |
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