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…

Anti-angiogenic drug loaded liposomes: Nanotherapy for early atherosclerotic lesions in mice.

Este artículo se encuentra disponible en la página web de la revista en la siguiente URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190540 También participan en la elaboración de este artículo científico: Aracely Calatayud-Pascual, Alicia López-Castellano, Elena P. Albelda, Enrique García-España, Luis Martí-Bonmatí, Juan C. Frias y M. Teresa Albelda. Fumagillin-loaded liposomes were injected into ApoE-KO mice. The animals were divided into several groups to test the efficacy of this anti-angiogenic drug for early treatment of atherosclerotic lesions. Statistical analysis of the lesions revealed a decrease in the lesion size after 5 weeks of treatment.

Recognition, Transformation, Detection of Nucleotides and Aqueous Nucleotide-Based Materials

Més enllà de la doble hèlix: L’estructura G-quàdruplex de l’ADN

L’ADN es la biomolecula fonamental per al correcte funcionament cel·lular i fins fa poc s’ha associat a l’estructura de doble helix descoberta fa mes de seixanta anys per Crick, Watson i Franklin. Tanmateix, s’han descrit altres estructures i conformacions diferents que l’ADN pot adoptar com els G-quadruplex. Aquests G-quadruplex es formen en regions del genoma riques en guanines amb una estructura tetramera i controlen processos biologics com l’expressio genetica, la proteccio contra l’envelliment o la transmissio de la informacio neuronal. En aquest article descrivim les seues caracteristiques quimiques i estructurals a mes d’introduir les seues principals funcions cel·lulars. Per finalit…

Zn2+ and Cu2+ complexes of a fluorescent scorpiand-type oxadiazole azamacrocyclic ligand: crystal structures, solution studies and optical properties

A ligand comprised of a macrocyclic pyridinophane core having a pendant arm containing a secondary amine group linked through a methylene spacer to a pyridyl–oxadiazole–phenyl (PyPD) fluorescent system has been prepared (L). The crystal structures of [ZnL](ClO4)2 and [CuL](ClO4)2 show that M2+ is coordinated to all the nitrogen atoms of the macrocyclic core, the secondary amine of the pendant arm and the nitrogen atom of the pyridine group of the fluorescent moiety, the latter bond being clearly weaker than the one with the pyridine of the macrocycle. Solution studies showed the formation of a highly stable Cu2+ complex with 1 : 1 stoichiometry, whereas with Zn2+ least stable complexes were…

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…

Binding Mode and Selectivity of a Scorpiand-Like Polyamine Ligand to Single- and Double-Stranded DNA and RNA: Metal- and pH-Driven Modulation

The interaction of a polyazacyclophane ligand having an ethylamine pendant arm functionalized with an anthryl group (L), with the single-stranded polynucleotides polyA, polyG, polyU, and polyC as well as with the double-stranded polynucleotides polyA-polyU, poly(dAT)(2), and poly(dGC)(2) has been followed by UV/Vis titration, steady state fluorescence spectroscopy, and thermal denaturation measurements. In the case of the single-stranded polynucleotides, the UV/Vis and fluorescence titrations permit to distinguish between sequences containing purine and pyrimidine bases. For the double-stranded polynucleotides the UV/Vis measurements show for all of them hypochromicity and bathochromic shif…

Cluster dirhenium(III) cis-dicarboxylates with α-amino acids ligands as mighty selective G4s binders.

The synthesis of four dirhenium(III) cis-dicarboxylates with the α-amino acids residues Asp (I), Glu (II), Phe (III) and Tyr (IV) is presented. The G-quadruplex stabilization potential was evaluated by fluorescence resonance energy transfer - melting analysis. All derivatives show specific binding to c-kit1 quadruplex, while II and IV have also strong stabilization activity to HTelo21 quadruplex. At the same time, the compounds do not show any stabilization activity for ds26 DNA, which suggests unique mechanisms of molecular DNA recognition for these complexes.

CCDC 1952561: Experimental Crystal Structure Determination

Related Article: Gianluca Ambrosi, M. Paz Clares, Isabel Pont, Mauro Formica, Vieri Fusi, Angela Ricci, Paola Paoli, Patrizia Rossi, Enrique García-España, Mario Inclán|2020|Dalton Trans.|49|1897|doi:10.1039/C9DT04764F

CCDC 1529591: Experimental Crystal Structure Determination

Related Article: Gianluca Ambrosi, M. Paz Clares, Isabel Pont, Mauro Formica, Vieri Fusi, Angela Ricci, Paola Paoli, Patrizia Rossi, Enrique García-España, Mario Inclán|2020|Dalton Trans.|49|1897|doi:10.1039/C9DT04764F