0000000000529589
AUTHOR
Ramon Vilar
Development of Polyamine‐Substituted Triphenylamine Ligands with High Affinity and Selectivity for G‐Quadruplex DNA
Currently, significant efforts are devoted to designing small molecules able to bind selectively to guanine quadruplexes (G4s). These noncanonical DNA structures are implicated in various important biological processes and have been identified as potential targets for drug development. Previously, a series of triphenylamine (TPA)-based compounds, including macrocyclic polyamines, that displayed high affinity towards G4 DNA were reported. Following this initial work, herein a series of second-generation compounds, in which the central TPA has been functionalised with flexible and adaptive linear polyamines, are presented with the aim of maximising the selectivity towards G4 DNA. The acid-bas…
Reversible Colorimetric Probes for Mercury Sensing
The selectivity and sensitivity of two colorimetric sensors based on the ruthenium complexes N719 [bis(2,2'-bipyridyl-4,4'-dicarboxylate)ruthenium(II) bis(tetrabutylammonium) bis(thiocyanate)] and N749 [(2,2':6',2' '-terpyridine-4,4',4' '-tricarboxylate)ruthenium(II) tris(tetrabutylammonium) tris(isothiocyanate)] are described. It was found that mercury ions coordinate reversibly to the sulfur atom of the dyes' NCS groups. This interaction induces a color change in the dyes at submicromolar concentrations of mercury. Furthermore, the color change of these dyes is selective for mercury(II) when compared with other ions such as lead(II), cadmium(II), zinc(II), or iron(II). The detection limit…
Aza-macrocyclic triphenylamine ligands for G-quadruplex recognition
A new series of triphenylamine-based ligands with one (TPA1PY), two (TPA2PY) or three pendant aza-macrocycle(s) (TPA3PY) has been synthesised and studied by means of pH-metric titrations, UV/Vis spectroscopy and fluorescence experiments. The affinity of these ligands for G-quadruplex (G4) DNA and the selectivity they show for G4s over duplex DNA were investigated by Forster resonance energy transfer (FRET) melting assays, fluorimetric titrations and circular dichroism spectroscopy. Interestingly, the interactions of the bi- and especially the tri-branched ligands with G4s lead to a very intense redshifted fluorescence emission band that may be associated with intermolecular aggregation betw…
Isotope fractionation of zinc in the paddy rice soil-water environment and the role of 2’deoxymugineic acid (DMA) as zincophore under Zn limiting conditions
Non-traditional stable isotope systems are increasingly used to study micronutrient cycling and acquisition in terrestrial ecosystems. We previously proposed for zinc (Zn) a conceptual model linking observed isotope signatures and fractionations to biogeochemical processes occurring in the rice soil environment and we suggested that 2’deoxymugineic acid (DMA) could play an important role for rice during the acquisition of Zn when grown under Zn limiting conditions. This proposition was sustained by the extent and direction of isotope fractionation observed during the complexation of Zn with DMA synthesised in our laboratory. Here we report a new set of experimental data from field and labor…
Visualising G-quadruplex DNA dynamics in live cells by fluorescence lifetime imaging microscopy
Guanine rich regions of oligonucleotides fold into quadruple-stranded structures called G-quadruplexes (G4s). Increasing evidence suggests that these G4 structures form in vivo and play a crucial role in cellular processes. However, their direct observation in live cells remains a challenge. Here we demonstrate that a fluorescent probe (DAOTA-M2) in conjunction with fluorescence lifetime imaging microscopy (FLIM) can identify G4s within nuclei of live and fixed cells. We present a FLIM-based cellular assay to study the interaction of non-fluorescent small molecules with G4s and apply it to a wide range of drug candidates. We also demonstrate that DAOTA-M2 can be used to study G4 stability i…