Interactions of Pt‐ttpy with G‐Quadruplexes Originating from Promoter Region of the c‐myc Gene Deciphered by NMR and Gel Electrophoresis Analysis |
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| Authors: | Dr. Marko Trajkovski Elodie Morel Dr. Florian Hamon Dr. Sophie Bombard Dr. Marie‐Paule Teulade‐Fichou Prof. Dr. Janez Plavec |
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| Affiliation: | 1. Slovenian NMR centre National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana (Slovenia);2. Institut Curie, Centre de Recherche, CNRS UMR9187‐INSERM U1196, Centre Universitaire Paris XI, Bat. 110, 91405 Orsay (France);3. UMR‐S INSERM 1007, Universite Paris Descartes, 45 Rue des Saint‐Peres, 75006 Paris (France);4. Faculty of Chemistry and Chemical Technology, University of Ljubljana, Askerceva cesta 5, 1000 Ljubljana (Slovenia);5. EN‐FIST, Centre of Excellence, Trg OF 13, 1000 Ljubljana (Slovenia) |
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| Abstract: | This study provides insights into the interactions of Pt‐ttpy, that is, a metallo‐organic heterocycle‐comprising platinum(II) complex of terpyridine, and G‐quadruplexes adopted by G‐rich DNA from the transcriptional regulatory element of the c‐myc gene, a well‐known attractive target for artificial modulation of oncogene expression. A previously noted drug‐like potential of Pt‐ttpy relies on its antiproliferative activity on cancer cells and its increased selectivity for G‐quadruplex binding attributed to the combination of distinct interacting modes. The predominant interaction between the herein used models of a parallel G‐quadruplex exhibiting short propeller‐type loops and Pt‐ttpy occurs through stacking to the outer G‐quartets. The presence of adenine versus thymine residue at the 5’‐end overhanging region allows the coordinative binding of Pt‐ttpy to the G‐quadruplex structure. Interestingly, Pt‐ttpy triggers the formation of the G‐quadruplex even in the absence of cations. Furthermore, NMR‐based characterisation revealed common structural features of Pt‐ttpy–G‐quadruplex complexes in the presence and absence of cations, which indicate that cations may be expelled from the cores of the corresponding structures. |
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| Keywords: | G‐quadruplexes ligands NMR spectroscopy platinum structures |
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