Organoplatinum(II) Complexes Self-Assemble and Recognize AT-Rich Duplex DNA Sequences

[Image: see text] The specific recognition of AT-rich DNA sequences opens up the door to promising diagnostic and/or therapeutic strategies against gene-related diseases. Here, we demonstrate that amphiphilic Pt(II) complexes of the type [Pt(dmba)(N∧N)]NO(3) (dmba = N,N-dimethylbenzylamine-κN, κC; N...

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Detalles Bibliográficos
Autores principales: Zamora, Ana, Wachter, Erin, Vera, María, Heidary, David K., Rodríguez, Venancio, Ortega, Enrique, Fernández-Espín, Vanesa, Janiak, Christoph, Glazer, Edith C., Barone, Giampaolo, Ruiz, José
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456496/
https://www.ncbi.nlm.nih.gov/pubmed/33502194
http://dx.doi.org/10.1021/acs.inorgchem.0c02648
Descripción
Sumario:[Image: see text] The specific recognition of AT-rich DNA sequences opens up the door to promising diagnostic and/or therapeutic strategies against gene-related diseases. Here, we demonstrate that amphiphilic Pt(II) complexes of the type [Pt(dmba)(N∧N)]NO(3) (dmba = N,N-dimethylbenzylamine-κN, κC; N∧N = dpq (3), dppz (4), and dppn (5)) recognize AT-rich oligonucleotides over other types of DNA, RNA, and model proteins. The crystal structure of 4 shows the presence of significant π-stacking interactions and a distorted coordination sphere of the d(8) Pt(II) atom. Complex 5, containing the largest π-conjugated ligand, forms supramolecular assemblies at high concentrations under aqueous environment. However, its aggregation can be promoted in the presence of DNA at concentrations as low as 10 μM in a process that “turns on” its excimer emission around 600 nm. Viscometry, gel electrophoresis, and theoretical calculations demonstrate that 5 binds to minor groove when self-assembled, while the monomers of 3 and 4 intercalate into the DNA. The complexes also inhibit cancer cell growth with low-micromolar IC(50) values in 2D tissue culture and suppress tumor growth in 3D tumor spheroids with a multicellular resistance (MCR) index comparable to that of cisplatin.