During the last years, our attention has focused on core-substituted naphthalene diimides (NDIs)1 as selective oligonucleotide ligands and fluorescent probes. In more detail, our research unit has shown that tri- and tetra-substituted NDIs are potent and reversible ligands as well as alkylating agents targeting guanine-rich oligonucleotides folded into G-quadruplex structures (G4s). G-rich sequences folding into G4 are present in biologically relevant proto-oncogenes and oncogene promoters as well as human telomeres and participate in biological processes crucial for cell survival. Consequently they represent a very appealing target and propelled the research for the development of new therapeutic approaches. 2 Interestingly, the optoelectronic properties of the NDI core can be effectively tuned by substitution as electron rich substituents on the aromatic core give origin to strong absorption and emission in the red spectroscopic window.1 We have prepared a library of water soluble compounds starting from the NDI core introducing amine substituents on the naphthalene unit. In order to overcome problems related to the cell membrane passage our idea was to exploit the affinity for G4 structures of NDIs and design a delivery system based on AS1411 as troian horse.3 We have studied the affinity of NDI compounds for AS1411 in G4 form, and characterized their complexes. We have evaluated the efficacy of AS1411 as NDI delivery tool on selected cell lines and studied cell internalization with time-resolved fluorescence confocal microscopy.
Water soluble naphthalenediimides as singlet oxygen sensitizers, fluorescence reporters and G-quadruplex ligands
F Manoli;I Manet
2014
Abstract
During the last years, our attention has focused on core-substituted naphthalene diimides (NDIs)1 as selective oligonucleotide ligands and fluorescent probes. In more detail, our research unit has shown that tri- and tetra-substituted NDIs are potent and reversible ligands as well as alkylating agents targeting guanine-rich oligonucleotides folded into G-quadruplex structures (G4s). G-rich sequences folding into G4 are present in biologically relevant proto-oncogenes and oncogene promoters as well as human telomeres and participate in biological processes crucial for cell survival. Consequently they represent a very appealing target and propelled the research for the development of new therapeutic approaches. 2 Interestingly, the optoelectronic properties of the NDI core can be effectively tuned by substitution as electron rich substituents on the aromatic core give origin to strong absorption and emission in the red spectroscopic window.1 We have prepared a library of water soluble compounds starting from the NDI core introducing amine substituents on the naphthalene unit. In order to overcome problems related to the cell membrane passage our idea was to exploit the affinity for G4 structures of NDIs and design a delivery system based on AS1411 as troian horse.3 We have studied the affinity of NDI compounds for AS1411 in G4 form, and characterized their complexes. We have evaluated the efficacy of AS1411 as NDI delivery tool on selected cell lines and studied cell internalization with time-resolved fluorescence confocal microscopy.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
