167 results found
Vilar R, Ruehl CL, Lim AHM, et al., 2019, An octahedral cobalt(III) complex with axial NH3 ligands that templates and selectively stabilises G-quadruplex DNA, Chemistry - A European Journal, Vol: 25, Pages: 9691-9700, ISSN: 0947-6539
Guanine-rich sequences of DNA are known to readily fold into tetra-stranded helical structures known as G-quadruplexes (G4). Due to their biological relevance, G4s are potential anticancer drug targets and therefore there is significant interest in molecules with high affinity for these structures. Most G4 binders are polyaromatic planar compounds which π-π stack on the G4's guanine tetrad. However, many of these compounds are not very selective since they can also intercalate into duplex DNA. Herein we report a new class of binder based on an octahedral cobalt(III) complex that binds to G4 via a different mode involving hydrogen-bonding, electrostatic interactions and π-π stacking. We show that this new compound binds selectivity to G4 over duplex DNA (particularly to the G-rich sequence of the c-myc promoter). This new octahedral complex also has the ability to template he formation of G4 DNA from the unfolded sequence. Finally, we show that upon binding to G4, the complex prevents helicase Pif1-p from unfolding the c-myc G4 structure.
Much of the functionality of multi-cellular systems arises from the spatial organisation and dynamic behaviours within and between cells. Current single-cell genomic methods only provide a transcriptional “snapshot” of individual cells. The real-time analysis and perturbation of living cells would generate a step-change in single-cellanalysis. Here we describe minimally invasive nanotweezers that can be spatially controlled to extract samples from living cells with single-molecule precision. They consist of two closely spaced electrodes with gaps as small as 10-20 nm, which can be usedfor the dielectrophoretic trapping of DNA and proteins.Aside from trapping single molecules, we also extract nucleic acids for gene expression analysis from living cells, without affecting their viability. Finally, we report on the trapping, and extraction of a single mitochondrion. This work bridges the gap between single-molecule/organelle manipulation and cell biology and can ultimately enable a better understanding of living cells.
Ferraro G, Pica A, Petruk G, et al., 2018, Preparation, structure, cytotoxicity and mechanism of action of ferritin-Pt(II) terpyridine compound nanocomposites, Nanomedicine, Vol: 13, Pages: 2995-3007, ISSN: 1743-5889
Aim: A Pt(II)-terpyridine compound, bearing two piperidine substituents at positions 2 and 2′ of the terpyridine ligand (1), is highly cytotoxic and shows a mechanism of action distinct from cisplatin. 1 has been incorporated within the ferritin nanocage (AFt). Materials & methods: Spectroscopic and crystallographic data of the Pt(II)–AFt nanocomposite have been collected and in vitro anticancer activity has been explored using cancer cells. Results: Pt(II)-containing fragments bind His49, His114 and His132. Pt(II)–AFt nanocomposite is less cytotoxic than 1, but it is more toxic than cisplatin at high concentrations. The Pt(II)–AFt nanocomposite triggers necrosis in cancer cells, as free 1 does. Conclusion: Pt(II)–AFt nanocomposites are promising vehicles to deliver Pt-based drugs to cancer cells.
Łęczkowska A, Gonzalez-Garcia J, Perez-Arnaiz C, et al., 2018, Binding studies of metal-salphen and metal-bipyridine complexes towards G-quadruplex DNA, Chemistry - A European Journal, Vol: 24, Pages: 11785-11794, ISSN: 0947-6539
The proposed in vivo formation of G-quadruplex DNA (G4 DNA) in promoter regions of oncogenes and in telomeres has prompted the development of small molecules with high affinity and selectivity for these structures. Herein we report the synthesis of a new di-substituted bipyridine ligand and the corresponding complexes with Ni2+ and VO2+ . Both these new complexes have been characterized spectroscopically and by X-ray crystallography. Detailed DNA binding studies of these two complexes, together with three previously reported metal salphen complexes, are presented. Using FRET melting assays, the binding affinity and selectivity of the five metal complexes against six different G4 DNA structures as well as a duplex DNA have been determined. In addition, we present detailed ITC and UV/Vis studies to characterize the interaction of the complexes with human telomeric G4 DNA. Finally, we show via a polymerase stop assay that these complexes are able to stabilize a G4 DNA structure (from the c-Myc oncogene promoter) and halt the activity of Taq polymerase.
Pont I, González-García J, Inclán M, et al., 2018, Aza-macrocyclic triphenylamine ligands for G-quadruplex recognition, Chemistry - A European Journal, Vol: 24, Pages: 10850-10858, ISSN: 0947-6539
A new series of triphenylamine-based ligands with one (TPA1PY), two (TPA2PY) or three pending aza-macrocycle(s) (TPA3PY) have 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 its selectivity over duplex DNA were investigated by FRET melting assays, fluorimetric titrations and circular dichroism (CD) spectroscopy. Interestingly, the interaction of the bi- and specially the tri-branched ligand with G4 leads to a very intense red-shifted fluorescence emission band which may be associated with intermolecular aggregation between the molecule and the DNA. This light-up effect allows the application of the ligands as fluorescence probes to selectivity detect G4.
Ferraro G, Marzo T, Infrasca T, et al., 2018, A case of extensive protein platination: the reaction of lysozyme with a Pt(ii)-terpyridine complex, Dalton Transactions, Vol: 47, Pages: 8716-8723, ISSN: 1477-9234
An antiproliferative platinum(ii)-terpyridine complex bearing two piperidine substituents at positions 2 and 2' (compound 1, hereafter) interacts non-covalently with DNA and induces cell death through necrosis, i.e. a mode of action that is distinct from that exhibited by cisplatin (Suntharalingam, et al., Metallomics, 2013, 5, 514). Here, the interaction between this Pt compound and the model protein hen egg white lysozyme (HEWL) was studied by both electrospray ionization mass spectrometry (ESI MS) and X-ray crystallography. The ESI MS data collected after 24 h protein incubation with compound 1 at two different pH values offer evidence that the metal complex degrades upon reaction with HEWL, forming adducts with 1 : 1, 2 : 1 and 3 : 1 Pt/protein ratios. Two different X-ray structures of Pt-protein adducts, obtained by the reaction of HEWL with the Pt compound under different experimental conditions and incubation times, are then reported. An unexpected extensive platination of the protein is clearly observed: Pt containing fragments bind close to the NZ atom of Lys1 and OE1 atom of Glu7, NE2 atom of His15 and NH1 atom of Arg14, ND1 atom of His15, NZ atom of Lys96, NZ atom of Lys97 and ND1 atom of Asn93, NZ atom of Lys13 and the C-terminal carboxylate, and the N-terminal amine. An additional binding site was observed close to the NZ atom of Lys33. These results suggest that both N- and C-terminal tails, as well as Lys side chains, have to be considered as potential binding sites of Pt-containing drugs. The peculiar reactivity of compound 1 with biological macromolecules could play a role in its mode of action.
Chan T, Morse S, Copping M, et al., 2018, Targeted delivery of DNA-Au nanoparticles across the blood-brain barrier using focused ultrasound, ChemMedChem, Vol: 13, Pages: 1311-1314, ISSN: 1860-7187
Nanoparticles have been widely studied as versatile platforms for in vivo imaging and therapy. However, their use to image and/or treat the brain is limited, as they are often unable to cross the blood–brain barrier (BBB). To overcome this problem, herein we report the use of focused ultrasound in vivo to successfully deliver DNA‐coated gold nanoparticles to specific locations in the brains of mice.
Rakers V, Cadinu P, Edel JB, et al., 2018, Development of microfluidic platforms for the synthesis of metal complexes and evaluation of their DNA affinity using online FRET melting assays, Chemical Science, Vol: 9, Pages: 3459-3469, ISSN: 2041-6520
Guanine-rich DNA sequences can fold into quadruple-stranded structures known as G-quadruplexes. These structures have been proposed to play important biological roles and have been identified as potential drug targets. As a result, there is increasing interest in developing small molecules that can bind to G-quadruplexes. So far, these efforts have been mostly limited to conventional batch synthesis. Furthermore, no quick on-line method to assess new G-quadruplex binders has been developed. Herein, we report on two new microfluidic platforms to: (a) readily prepare G-quadruplex binders (based on metal complexes) in flow, quantitatively and without the need for purification before testing; (b) a microfluidic platform (based on FRET melting assays of DNA) that enables the real-time and on-line assessment of G-quadruplex binders in continuous flow.
Vilar R, 2018, Nucleic acid quadruplexes and metallo-drugs, Metallo-Drugs: Development and Action of Anticancer Agents, Pages: 325-349, ISBN: 9783110469844
© Walter de Gruyter GmbH, Berlin, Germany 2018. Guanine-rich sequences of DNA can readily fold into tetra-stranded helical assemblies known as G-quadruplexes (G4s). It has been proposed that these structures play important biological roles in transcription, translation, replication, and telomere maintenance. Therefore, over the past 20 years they have been investigated as potential drug targets for small molecules including metal complexes. This chapter provides an overview of the different classes of metal complexes as G4-binders and discusses the application of these species as optical probes for G-quadruplexes as well as metallo-drugs.
Vilar R, 2018, Nucleic Acid Quadruplexes and Metallo-Drugs., Met Ions Life Sci, Vol: 18, ISSN: 1559-0836
Guanine-rich sequences of DNA can readily fold into tetra-stranded helical assemblies known as G-quadruplexes (G4s). It has been proposed that these structures play important biological roles in transcription, translation, replication, and telomere maintenance. Therefore, over the past 20 years they have been investigated as potential drug targets for small molecules including metal complexes. This chapter provides an overview of the different classes of metal complexes as G4-binders and discusses the application of these species as optical probes for G-quadruplexes as well as metallo-drugs.
Bandeira S, Gonzalez-Garcia J, Pensa E, et al., 2018, A Redox-Activated G-Quadruplex DNA Binder Based on a Platinum(IV)-Salphen Complex, Angewandte Chemie, Vol: 130, Pages: 316-319, ISSN: 0044-8249
Cowell S, Carroll L, Lavdas I, et al., 2017, Towards an MMP-2-activated molecular agent for cancer imaging, Dalton Transactions, Vol: 47, Pages: 1530-1534, ISSN: 1477-9234
Matrix metalloproteinases (MMPs) have been identified as biomarkers for cancer, offering prognostic potential; however, non-invasive detection protocols are currently lacking. Herein, we describe the synthesis of a DOTA-containing peptide sequence that can be radiolabelled easily with 68Gallium or can be incorporated with gadolinium for possible MRI applications with clear selectivity for MMP-2 over other members of the MMP family, giving MMP-2 selective cleavage of the labelled peptides.
Vilar R, Bandeira S, Gonzalez Garcia J, et al., 2017, A redox-activated G-quadruplex DNA binder based on a platinum(IV)-salphen complex., Angewandte Chemie International Edition, Vol: 57, Pages: 310-313, ISSN: 1521-3757
There has been increasing interest in the development of small molecules that can selectively bind to G-quadruplex DNA structures. The latter have been associated to a number of key biological processes and therefore are proposed to be potential targets for drug development. In this paper we report the first example of a reduction-activated G-quadruplex DNA binder. We show that a new octahedral platinum(IV)-salphen complex does not interact with DNA in aqueous media at pH 7.4; however, upon addition of bio-reductants such as ascorbic acid or glutathione, the compound readily reduces to the corresponding square planar platinum(II) complex. In contrast to the parent platinum(IV) complex, the in situ generated platinum(II) complex binds to HTelo and c-Myc G-quadruplex DNA with affinity constants up to 106 M-1.
Pyne ALB, Hoogenboom BW, Vilar R, et al., 2017, Visualisation of DNA conformational changes in situ at nanometre resolution, 19th IUPAB Congress / 11th EBSA Congress, Publisher: SPRINGER, Pages: S369-S369, ISSN: 0175-7571
Gonzalez-Garcia J, Vilar R, 2017, Supramolecular Principles for Small Molecule Binding to DNA Structures, Comprehensive Supramolecular Chemistry II, Pages: 39-70, ISBN: 9780128031995
© 2017 Elsevier Ltd. All rights reserved. Small molecules that interact with deoxyribonucleic acid (DNA) are important for the development of drugs and biomolecular tools. There are indeed several drugs in clinical use whose main biological target is DNA; likewise, a range of optical probes that bind to DNA are routinely used to study biological systems. Therefore, understanding, rationalizing, and predicting the interaction of small molecules with DNA is an important area of research. This article provides an overview of the key noncovalent interactions used by small organic and metal-organic molecules to bind to DNA. The first part of the article provides an overview of the different DNA structures/topologies and the key supramolecular interactions they display. The subsequent sections of the article have been divided by the type of DNA structure that is being targeted as well as by the binding mode displayed by the molecules discussed. Rather than providing an exhaustive and comprehensive review of the very extensive literature, the main aim of this article is to highlight the key supramolecular principles that drive these interactions.
Cilibrizzi A, Fedorova M, Collins J, et al., 2017, A tri-functional vanadium(IV) complex to detect cysteine oxidation, DALTON TRANSACTIONS, Vol: 46, Pages: 6994-7004, ISSN: 1477-9226
The development of effective molecular probes to detect and image the levels of oxidative stress in cells remains a challenge. Herein we report the design, synthesis and preliminary biological evaluation of a novel optical probe to monitor oxidation of thiol groups in cysteine-based phosphatases (CBPs). Following orthogonal protecting approaches we synthesised a new vanadyl complex designed to bind to CBPs. This complex is functionalised with a well-known dimedone derivative (to covalently trap sulfenic acids, SOHs) and a coumarin-based fluorophore for optical visualization. We show that this new probe efficiently binds to a range of phosphatases in vitro with nanomolar affinity. Moreover, preliminary flow cytometry and microscopy studies in live HCT116 cells show that this probe can successfully image cellular levels of sulfenic acids – one of the species resulting from protein oxidative damage.
Cilibrizzi A, Terenghi M, Fedorova M, et al., 2017, Small-molecule optical probes for cell imaging of protein sulfenylation and their application to monitor cisplatin induced protein oxidation, Sensors and Actuators B: Chemical, Vol: 248, Pages: 437-446, ISSN: 0925-4005
Reactive oxygen species (ROS) are considered versatile second messengers mediating fundamental biological functions. A molecular pathway by which ROS determine functional diversity is the selective oxidation of cysteine residues to form sulfenic acid (SOH) products, known as sulfenylation or S-hydroxylation. This crucial post-translational modification is responsible for the alteration of protein stability, function and signalling. Despite considerable advances on the identification of sulfenic residues on individual proteins, improved methods are needed for direct visualization and accurate quantification of the extent of total protein sulfenylation. Herein we present the synthesis of two new cell-permeable fluorescent probes containing dimedone (a cyclic β-diketone with high specificity for sulfenic acids), and apply them to study oxidation processes in individual cells via microscopy. The low cytotoxicity, cell permeability and optical features of the probes allowed us to visualize and quantify the oxidation of cysteine residues in live cells during H2O2-mediated oxidative burst (i.e. exogenously administered H2O2). We present preliminary cellular imaging studies with these probes to analyse the oxidation process in cells treated with the anticancer drug cisplatin.
Zhou CQ, Liao TC, Li ZQ, et al., 2017, Di-nickel-salphen complexes as binders of human telomeric dimeric G-quadruplexes, Chemistry - A European Journal, Vol: 23, Pages: 4713-4722, ISSN: 0947-6539
Three new polyether-tethered di-nickel-salphen complexes (2a-c) have been synthesized and fully characterized by NMR spectroscopy, mass spectrometry and elemental analyses. The binding affinity and selectivity of these complexes and of the parent mono-nickel complex (1) towards dimeric quadruplex DNA have been determined by UV-Vis titrations, fluorescence spectroscopy, CD spectroscopy and electrophoresis. These studies have shown that the di-nickel-salphen complex with the longest polyether linker (2c) has higher binding affinity and selectivity towards dimeric quadruplexes (over monomeric quadruplexes) than the di-nickel-salphen complexes with the shorter polyether linkers (2a and 2b). Complex 2c also has higher selectivity towards human telomeric dimeric quadruplexes with one TTA linker than the monometallic complex 1. Based on the spectroscopic data, a possible binding mode between complex 2c and the dimeric G-quadruplex DNA under study is proposed.
Vilar Compte R, Wilson N, Mak LH, et al., 2016, A lipophilic copper(II) complex as an optical probe for intracellular detection of NO, Dalton Transactions, Vol: 45, Pages: 18177-18182, ISSN: 1477-9226
A new chemical sensor for cellular imaging of NO is presented. This cell-permeable probe is based on a complex where copper(II) is coordinated to a tridentate ligand substituted with a fluorophore (NBD) and an octyl group. The fluorescent response of this complex towards a range of reactive species (namely NO, NO2-, NO3-, H2O2, ClO-, O2-and ONOO-) has been studied in vitroshowing that the probe is highly selective for NO. The probe is readily taken up by cells and is able to image the cellular concentrations of NO
Vilar Compte R, Klejevskaja B, Pyne LBA, et al., 2016, Studies of G-quadruplexes formed within self-assembled DNA mini-circles, Chemical Communications (London), Vol: 52, Pages: 12454-12457, ISSN: 0009-241X
We have developed self-assembled DNA mini-circles that contain a G-quadruplex-forming sequence from the c-Myc oncogene promoter and demonstrate by FRET that the G-quadruplex unfolding kinetics are 10-fold slower than for the simpler 24-mer G-quadruplex that is commonly used for FRET experiments.
Markovic T, Manzoor S, Humphreys-Williams E, et al., 2016, Experimental determination of zinc isotope fractionation in complexes with the phytosiderophore 2’-deoxymugeneic acid (DMA) and its structural analogues, and implications for plant uptake mechanisms, Environmental Science & Technology, Vol: 51, Pages: 98-107, ISSN: 0013-936X
The stable isotope signatures of zinc are increasingly used to study plant and soil processes. Complexation with phytosiderophores is a key process and understanding the controls of isotope fractionation is central to such studies. Here, we investigated isotope fractionation during complexation of Zn2+ with the phytosiderophore 2’-deoxymugeneic acid (DMA) - which we synthesised - and with three commercially-available structural analogues of DMA: EDTA, TmDTA and CyDTA. We used ion exchange chromatography to separate free and complexed zinc, and identified appropriate cation exchange resins for the individual systems. These were Chelex-100 for EDTA and CyDTA, Amberlite CG50 for TmDTA and Amberlite IR120 for DMA. With all the ligands we found preferential partitioning of isotopically heavy zinc in the complexed form, and the extent of fractionation was independent of the Zn:ligand ratio used, indicating isotopic equilibrium and that the results were not significantly affected by artefacts during separation. The fractionations (in ‰) were +0.33 ± 0.07 (1, n=3), +0.45 ± 0.02 (1, n=2), +0.62 ± 0.05 (1, n=3) and +0.30 ± 0.07 (1, n=4) for EDTA, TmDTA, CyDTA and DMA, respectively. Despite the similarity in Zn-coordinating donor groups, the fractionation factors are significantly different and extent of fractionation seems proportional to the complexation stability constant. The extent of fractionation with DMA agreed with observed fractionations in zinc uptake by paddy rice in field experiments, supporting the possible involvement of DMA in zinc uptake by rice.
Kotar A, Wang B, Shivalingam A, et al., 2016, NMR Structure of a Triangulenium based Long-lived Fluorescence Probe Bound to G-quadruplex, Angewandte Chemie - International Edition, Vol: 55, Pages: 12508-12511, ISSN: 1433-7851
An NMR structural study of the interaction between a small-molecule opticalprobe (DAOTA-M2) and a G-quadruplex from the promoter region of c-myc oncogenedemonstrates their interaction at 1:2 binding stoichiometry. NMR restrained structuralcalculations show that binding of DAOTA-M2 occurs mainly through the π-π stackingbetween the polyaromatic core of the ligand and guanine residues of the outer G-quartets.Interestingly, the binding affinities of DAOTA-M2 to the outer G-quartets of theunimolecular parallel G-quadruplex under study differ by a factor of two. Unrestrained MDcalculations indicate that DAOTA-M2 displays significant dynamic behavior when stackedon a G-quartet plane. These studies provide molecular guidelines for design of trianguleniumderivatives that can be used as optical probes of G-quadruplexes.
Vilar Compte R, Collins J, Woscholski R, et al., 2016, Vanadyl complexes with dansyl-labelled di-picolinic acid ligands: synthesis, phosphatase inhibition activity and cellular uptake studies, Dalton Transactions, Vol: 45, Pages: 7104-7113, ISSN: 1477-9226
Vanadium complexes have been previously utilised as potent inhibitors of cysteine based phosphatases (CBPs) . Herein, we present the synthesis and characterisation of two new fluorescently labelled vanadyl complexes (14 and 15 ) with bridged dipicolinic acid ligand. These compounds differ significantly from previous vanadyl complexes with phosphatase inhibition properties in that the metal-chelating part is a single tetradentate unit, which should afford greater stability and scope for synthetic elaboration then the earlier complexes. These new complexes inhibit a selection of cysteine based phosphatases (CBPs) in the nM range with some selectivity. Fluorescence spectroscopic studies (including fluorescence anisotropy) were carried out to demonstrate that the complexes are not simply acting as vanadyl delivery vehicles but they interact with the proteins. Finally, we present preliminary fluorescence microscopy studies to demonstrate that the complexes are cell permeable and localise throughout the cytoplasm of NIH3T3 cells.
Gama S, Rodrigues I, Mendes F, et al., 2016, Anthracene-terpyridine metal complexes as new G-quadruplex DNA binders, Journal of Inorganic Biochemistry, Vol: 160, Pages: 275-286, ISSN: 1873-3344
The formation of quadruple-stranded DNA induced by planar metal complexes has particular interest in the development of novel anticancer drugs. This is especially relevant for the inhibition of telomerase, which plays an essential role in cancer cell immortalization and is overexpressed in ca. 85-90% of cancer cells. Moreover, G-quadruplexes also exist in other locations in the human genome, namely oncogene promoter regions, and it has been hypothesized that they play a regulatory role in gene transcription. Herein we report a series of new anthracene-containing terpyridine ligands and the corresponding Cu(II) and Pt(II) complexes, with different linkers between the anthracenyl moiety and the terpyridine chelating unit. The interaction of these ligands and metal complexes with different topologies of DNA was studied by several biophysical techniques. The Pt(II) and Cu(II) complexes tested showed affinity for quadruplex-forming sequences with a good selectivity over duplex DNA. Importantly, the free ligands do not have significant affinity for any of the DNA sequences used, which shows that the presence of the metal is essential for high affinity (and selectivity). This effect is more evident in the case of the Pt(II) complexes. Moreover, the presence of a longer linker between the chelating terpyridine unit and the anthracene moiety enhances the interaction with G-quadruplex-forming sequences. We further evaluated the ability of the Cu(II) complexes to interact with, and stabilize G-quadruplex containing regions in oncogene promoters via a polymerase stop assay. These studies indicated that the metal complexes are able to induce G-quadruplex formation and stop polymerase activity.
Vilar Compte R, Shivalingam A, Vysniauskas A, et al., 2016, Trianguleniums as optical probes for G-quadruplexes: A photophysical, electrochemical and computational study, Chemistry - A European Journal, Vol: 22, Pages: 4129-4139, ISSN: 0947-6539
Nucleic acids can adopt non-duplex topologies such as G-quadruplexes in vitro. Yet it hasbeen challenging to establish their existence and function in vivo due to a lack of suitabletools. Recently, we identified the triangulenium compound DAOTA-M2 as a uniquefluorescence probe for such studies. This probe’s emission lifetime is highly dependent onthe topology of the DNA it interacts with opening up the possibility of carrying out live cellimaging studies. Herein we describe the origin of its fluorescence selectivity for Gquadruplexes.Cyclic voltammetry predicts that the appended morpholino groups can act asintra-molecular photo-induced electron transfer (PET) quenchers. Photophysical studies showthat a delicate balance between this effect and inter-molecular PET with nucleobases is key tothe overall fluorescence enhancement observed upon nucleic acid binding. We utilisedcomputational modelling to demonstrate a conformational dependence of intra-molecularPET. Finally, we performed orthogonal studies with a triangulenium compound where themorpholino groups were removed and demonstrate that this change inverts trianguleniumfluorescence selectivity from G-quadruplex to duplex DNA, thus highlighting the importanceof fine-tuning the molecular structure not only for target affinity but also for fluorescenceresponse.
Ang DL, Harper BWJ, Cubo L, et al., 2016, Quadruplex DNA-Stabilising Dinuclear Platinum(II) Terpyridine Complexes with Flexible Linkers, CHEMISTRY-A EUROPEAN JOURNAL, Vol: 22, Pages: 2317-2325, ISSN: 0947-6539
Ang DL, Harper BWJ, Cubo L, et al., 2016, Back Cover: Quadruplex DNA-Stabilising Dinuclear Platinum(II) Terpyridine Complexes with Flexible Linkers (Chem. Eur. J. 7/2016), Chemistry - A European Journal, Vol: 22, Pages: 2540-2540, ISSN: 0947-6539
Turek VA, Francescato Y, Cadinu P, et al., 2015, Self-Assembled Spherical Supercluster Metamaterials from Nanoscale Building Blocks, ACS Photonics, Vol: 3, Pages: 35-42, ISSN: 2330-4022
We report on a simple, universal and large scale self-assembly method for generation of spherical superclusters from nanoscopic building blocks. The fundamentals of this approach relies on the ultra-high pre-concentration of nanoparticles (NP) followed by either using emulsification strategies or alternatively multiphase microfluidic microdroplets. In both cases drying of the NP droplets yield highly spherical self-assembled superclusters with unique optical properties. We demonstrate that the behaviour of these spheres can be controlled by surface functionalization before and after the self-assembly process. These structures show unique plasmonic collective response both on the surface and within the supercluster in the visible and infrared regions. Furthermore, we demonstrate that these strong, tunable optical modes can be used towards ultra-sensitive, reproducible, surface-enhanced spectroscopies.
Mion G, Gianferrara T, Bergamo A, et al., 2015, Phototoxic Activity and DNA Interactions of Water-Soluble Porphyrins and Their Rhenium(I) Conjugates, CHEMMEDCHEM, Vol: 10, Pages: 1901-1914, ISSN: 1860-7179
Shivalingam A, Izquierdo MA, Le Marois A, et al., 2015, The interactions between a small molecule and G-quadruplexes are visualised by fluorescence lifetime imaging microscopy, Nature Communications, Vol: 6, ISSN: 2041-1723
Guanine-rich oligonucleotides can fold into quadruple-stranded helical structures known as G-quadruplexes. Mounting experimental evidence has gathered suggesting that these non-canonical nucleic acid structures form in vivo and play essential biological roles. However, to date, there are no small-molecule optical probes to image G-quadruplexes in live cells. Herein, we report the design and development of a small fluorescent molecule, which can be used as an optical probe for G-quadruplexes. We demonstrate that the fluorescence lifetime of this new probe changes considerably upon interaction with different nucleic acid topologies. Specifically, longer fluorescence lifetimes are observed in vitro for G-quadruplexes than for double- and single-stranded nucleic acids. Cellular studies confirm that this molecule is cell permeable, has low cytotoxicity and localizes primarily in the cell nucleus. Furthermore, using fluorescence lifetime imaging microscopy, live-cell imaging suggests that the probe can be used to study the interaction of small molecules with G-quadruplexes in vivo.
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