38 results found
Di Antonio M, Ponjavic A, Radzevičius A, et al., 2020, Single-molecule visualization of DNA G-quadruplex formation in live cells., Nat Chem
Substantial evidence now exists to support that formation of DNA G-quadruplexes (G4s) is coupled to altered gene expression. However, approaches that allow us to probe G4s in living cells without perturbing their folding dynamics are required to understand their biological roles in greater detail. Herein, we report a G4-specific fluorescent probe (SiR-PyPDS) that enables single-molecule and real-time detection of individual G4 structures in living cells. Live-cell single-molecule fluorescence imaging of G4s was carried out under conditions that use low concentrations of SiR-PyPDS (20 nM) to provide informative measurements representative of the population of G4s in living cells, without globally perturbing G4 formation and dynamics. Single-molecule fluorescence imaging and time-dependent chemical trapping of unfolded G4s in living cells reveal that G4s fluctuate between folded and unfolded states. We also demonstrate that G4 formation in live cells is cell-cycle-dependent and disrupted by chemical inhibition of transcription and replication. Our observations provide robust evidence in support of dynamic G4 formation in living cells.
Minard A, Morgan D, Raguseo F, et al., 2020, A short peptide that preferentially binds c-MYC G-quadruplex DNA., Chem Commun (Camb)
G-quadruplexes (G4s) are non-canonical DNA secondary structures. The identification of selective tools to probe individual G4s over the ∼700 000 found in the human genome is key to unravel the biological significance of specific G4s. We took inspiration from a crystal structure of the bovine DHX36 helicase bound to the G4 formed in the promoter region of the oncogene c-MYC to identify a short peptide that preferentially binds MYC G4 with nM affinity over a small panel of parallel and non-parallel G4s tested.
Chung BYW, Balcerowicz M, Di Antonio M, et al., 2020, An RNA thermoswitch regulates daytime growth in Arabidopsis, NATURE PLANTS, Vol: 6, Pages: 522-+, ISSN: 2055-026X
Raguseo F, Chowdhury S, Minard A, et al., 2020, Chemical-biology approaches to probe DNA and RNA G-quadruplex structures in the genome, CHEMICAL COMMUNICATIONS, Vol: 56, Pages: 1317-1324, ISSN: 1359-7345
Weber J, Bollepalli L, Belenguer AM, et al., 2019, An Activatable Cancer-Targeted Hydrogen Peroxide Probe for Photoacoustic and Fluorescence Imaging, CANCER RESEARCH, Vol: 79, Pages: 5407-5417, ISSN: 0008-5472
Di Antonio M, Minard A, Liano D, et al., 2019, The unexplored potential of quinone methides in chemical biology, Bioorganic and Medicinal Chemistry, Vol: 27, Pages: 2298-2305, ISSN: 0968-0896
Quinone methides (QMs) are transient reactive species that can be efficiently generated from stable precursors under a variety of biocompatible conditions. Due to their electrophilic nature, QMs have been widely explored as cross-linking agents of DNA and proteins under physiological conditions. However, QMs also have a diene character and can irreversibly react via Diels-Alder reaction with electron-rich dienophiles. This particular reactivity has been recently exploited to label biomolecules with fluorophores in living cells.QMs are characterised by two unique properties that make them ideal candidates for chemical biology applications: i) they can be efficiently generated in situ from very stable precursors by means of bio-orthogonal protocols ii) they are reversible cross-linking agents, making them suitable for “catch and release” target-enrichment experiments. Nevertheless, there are only few examples reported to date that truly take advantage of QMs unique chemistry in the context of chemical-biology assay development. In this review, we will examine the most relevant examples that illustrate the benefit of using QMs for chemical biology purposes and we will anticipate novel approaches to further their applications in biologically relevant contexts.
Marsico G, Chambers VS, Sahakyan AB, et al., 2019, Whole genome experimental maps of DNA G-quadruplexes in multiple species, Nucleic Acids Research, Vol: 47, Pages: 3862-3874, ISSN: 0305-1048
Genomic maps of DNA G-quadruplexes (G4s) can help elucidate the roles that these secondary structures play in various organisms. Herein, we employ an improved version of a G-quadruplex sequencing method (G4-seq) to generate whole genome G4 maps for 12 species that include widely studied model organisms and also pathogens of clinical relevance. We identify G4 structures that form under physiological K+ conditions and also G4s that are stabilized by the G4-targeting small molecule pyridostatin (PDS). We discuss the various structural features of the experimentally observed G-quadruplexes (OQs), highlighting differences in their prevalence and enrichment across species. Our study describes diversity in sequence composition and genomic location for the OQs in the different species and reveals that the enrichment of OQs in gene promoters is particular to mammals such as mouse and human, among the species studied. The multi-species maps have been made publicly available as a resource to the research community. The maps can serve as blueprints for biological experiments in those model organisms, where G4 structures may play a role.
Sengar A, Vandana JJ, Chambers VS, et al., 2019, Structure of a (3+1) hybrid G-quadruplex in the PARP1 promoter, NUCLEIC ACIDS RESEARCH, Vol: 47, Pages: 1564-1572, ISSN: 0305-1048
Mao S-Q, Ghanbarian AT, Spiegel J, et al., 2018, DNA G-quadruplex structures mold the DNA methylome, NATURE STRUCTURAL & MOLECULAR BIOLOGY, Vol: 25, Pages: 951-+, ISSN: 1545-9993
Greenfield JL, Evans EW, Di Nuzzo D, et al., 2018, Unraveling Mechanisms of Chiral Induction in Double-Helical Metallopolymers, Journal of the American Chemical Society, Vol: 140, Pages: 10344-10353, ISSN: 0002-7863
© 2018 American Chemical Society. Self-assembled helical polymers hold great promise as new functional materials, where helical handedness controls useful properties such as circularly polarized light emission or electron spin. The technique of subcomponent self-assembly can generate helical polymers from readily prepared monomers. Here we present three distinct strategies for chiral induction in double-helical metallopolymers prepared via subcomponent self-assembly: (1) employing an enantiopure monomer, (2) polymerization in a chiral solvent, (3) using an enantiopure initiating group. Kinetic and thermodynamic models were developed to describe the polymer growth mechanisms and quantify the strength of chiral induction, respectively. We found the degree of chiral induction to vary as a function of polymer length. Ordered, rod-like aggregates more than 70 nm long were also observed in the solid state. Our findings provide a basis to choose the most suitable method of chiral induction based on length, regiochemical, and stereochemical requirements, allowing stereochemical control to be established in easily accessible ways.
Sahakyan AB, Chambers VS, Marsico G, et al., 2017, Machine learning model for sequence-driven DNA G-quadruplex formation, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322
Hansel-Hertsch R, Di Antonio M, Balasubramanian S, 2017, DNA G-quadruplexes in the human genome: detection, functions and therapeutic potential, NATURE REVIEWS MOLECULAR CELL BIOLOGY, Vol: 18, Pages: 279-284, ISSN: 1471-0072
Nieto-Orellana A, Di Antonio M, Conte C, et al., 2017, Effect of polymer topology on non-covalent polymer-protein complexation: miktoarm versus linear mPEG-poly(glutamic acid) copolymers, POLYMER CHEMISTRY, Vol: 8, Pages: 2210-2220, ISSN: 1759-9954
Xu H, Di Antonio M, McKinney S, et al., 2017, CX-5461 is a DNA G-quadruplex stabilizer with selective lethality in BRCA1/2 deficient tumours, NATURE COMMUNICATIONS, Vol: 8, ISSN: 2041-1723
Nicoli F, Roos MK, Hemmig EA, et al., 2016, Proximity-Induced H-Aggregation of Cyanine Dyes on DNA-Duplexes, JOURNAL OF PHYSICAL CHEMISTRY A, Vol: 120, Pages: 9941-9947, ISSN: 1089-5639
Hansel-Hertsch R, Beraldi D, Lensing SV, et al., 2016, G-quadruplex structures mark human regulatory chromatin, NATURE GENETICS, Vol: 48, Pages: 1267-1272, ISSN: 1061-4036
Chambers VS, Marsico G, Boutell JM, et al., 2015, High-throughput sequencing of DNA G-quadruplex structures in the human genome, NATURE BIOTECHNOLOGY, Vol: 33, Pages: 877-+, ISSN: 1087-0156
Yangyuoru PM, Di Antonio M, Ghimire C, et al., 2015, Dual Binding of an Antibody and a Small Molecule Increases the Stability of TERRA G-Quadruplex, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 54, Pages: 910-913, ISSN: 1433-7851
Yangyuoru PM, DiAntonio M, Ghimire C, et al., 2015, Dual Binding of an Antibody and a Small Molecule Increases the Stability of TERRA G-Quadruplex, Angewandte Chemie, Vol: 127, Pages: 924-927, ISSN: 0044-8249
Le DD, Di Antonio M, Chan LKM, et al., 2015, G-quadruplex ligands exhibit differential G-tetrad selectivity, CHEMICAL COMMUNICATIONS, Vol: 51, Pages: 8048-8050, ISSN: 1359-7345
Di Antonio M, McLuckie KIE, Balasubramanian S, 2014, Reprogramming the Mechanism of Action of Chlorambucil by Coupling to a G-Quadruplex Ligand, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 136, Pages: 5860-5863, ISSN: 0002-7863
Biffi G, Di Antonio M, Tannahill D, et al., 2014, Visualization and selective chemical targeting of RNA G-quadruplex structures in the cytoplasm of human cells, NATURE CHEMISTRY, Vol: 6, Pages: 75-80, ISSN: 1755-4330
Di Antonio M, 2014, Quinone Methides Generation: Applications in Chemical Biology, CURRENT ORGANIC CHEMISTRY, Vol: 18, Pages: 2-2, ISSN: 1385-2728
McLuckie KIE, Di Antonio M, Zecchini H, et al., 2013, G-Quadruplex DNA as a Molecular Target for Induced Synthetic Lethality in Cancer Cells, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 135, Pages: 9640-9643, ISSN: 0002-7863
Mitchell T, Ramos-Montoya A, Di Antonio M, et al., 2013, Downregulation of Androgen Receptor Transcription by Promoter G-Quadruplex Stabilization as a Potential Alternative Treatment for Castrate-Resistant Prostate Cancer, BIOCHEMISTRY, Vol: 52, Pages: 1429-1436, ISSN: 0006-2960
Murat P, Gormally MV, Sanders D, et al., 2013, Light-mediated in cell downregulation of G-quadruplex-containing genes using a photo-caged ligand, CHEMICAL COMMUNICATIONS, Vol: 49, Pages: 8453-8455, ISSN: 1359-7345
Nikan M, Di Antonio M, Abecassis K, et al., 2013, An Acetylene-Bridged 6,8-Purine Dimer as a Fluorescent Switch-On Probe for Parallel G-Quadruplexes, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, Vol: 52, Pages: 1428-1431, ISSN: 1433-7851
Di Antonio M, Rodriguez R, Balasubramanian S, 2012, Experimental approaches to identify cellular G-quadruplex structures and functions, METHODS, Vol: 57, Pages: 84-92, ISSN: 1046-2023
Doria F, Nadai M, Folini M, et al., 2012, Hybrid ligand-alkylating agents targeting telomeric G-quadruplex structures, ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 10, Pages: 2798-2806, ISSN: 1477-0520
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