RNA therapeutics; antisense agents; oligonucleotides; DNA diagnostics; hydrophobic bases; RNA damage; charge transport; siRNA; RNA; DNA; antisense; abasic RNA
Schuermann David, Scheidegger Simon P., Weber Alain R., Bjørås Magnar, Leumann Christian J., Schär Primo (2016), 3CAPS – a structural AP–site analogue as a tool to investigate DNA base excision repair, in Nucleic Acids Research
, 44, 2187-2198.
Hari Yvonne, Dugovič Branislav, Istrate Alena, Fignolé Annabel, Leumann Christian J., Schürch Stefan (2016), The Contribution of the Activation Entropy to the Gas-Phase Stability of Modified Nucleic Acid Duplexes, in Journal of the American Society for Mass Spectrometry
, 27, 1186-1196.
Goyenvalle Aurelie, Leumann Christian, Garcia Luis (2016), Therapeutic Potential of Tricyclo-DNA antisense oligonucleotides, in Journal of Neuromuscular Diseases
, 3, 157-167.
Roethlisberger P., Istrate A., Marcaida Lopez M. J., Visini R., Stocker A., Reymond J. L., Leumann C. J. (2016), X-ray structure of a lectin-bound DNA duplex containing an unnatural phenanthrenyl pair, in Chemical Communications
, 52, 4749-4752.
Istrate Alena, Medvecky Michal, Leumann Christian J. (2015), 2′-Fluorination of Tricyclo-DNA Controls Furanose Conformation and Increases RNA Affinity, in Organic Letters
, 17, 1950-1953.
Goyenvalle Aurelie, Griffith Graziella, Babbs Arran, Andaloussi Samir El, Ezzat Kariem, Avril Aurelie, Dugovic Branislav, Chaussenot Remi, Ferry Arnaud, Voit Thomas, Amthor Helge, Buhr Claudia, Schurch Stefan, Wood Matthew J. A., Davies Kay E., Vaillend Cyrille, Leumann Christian, Garcia Luis (2015), Functional correction in mouse models of muscular dystrophy using exon-skipping tricyclo-DNA oligomers, in Nat Med
, 21, 270-275.
Ezzat Kariem, Aoki Yoshitsugu, Koo Taeyoung, McClorey Graham, Benner Leif, Coenen-Stass Anna, O’Donovan Liz, Lehto Taavi, Garcia-Guerra Antonio, Nordin Joel, Saleh Amer F., Behlke Mark, Morris John, Goyenvalle Aurelie, Dugovic Branislav, Leumann Christian, Gordon Siamon, Gait Michael J., El−Andaloussi Samir, Wood Matthew J. A. (2015), Self-Assembly into Nanoparticles Is Essential for Receptor Mediated Uptake of Therapeutic Antisense Oligonucleotides, in Nano Letters
, 15, 4364-4373.
Medvecky Michal, Istrate Alena, Leumann Christian J. (2015), Synthesis and Properties of 6′-Fluoro-tricyclo-DNA, in Journal of Organic Chemistry
, 80, 3556-3565.
Calabretta Alessandro, Küpfer Pascal A., Leumann Christian J. (2015), The effect of RNA base lesions on mRNA translation, in Nucleic Acids Research
, 43, 4713-4720.
Dugovic Branislav, Leumann Christian J. (2014), A 6′-Fluoro-Substituent in Bicyclo-DNA Increases Affinity to Complementary RNA Presumably by CF–HC Pseudohydrogen Bonds, in Journal of Organic Chemistry
, 79, 1271-1279.
Küpfer PascalA, Leumann ChristianJ (2014), Oxidative Damage on RNA Nucleobases, in Erdmann Volker (ed.), Springer, Berlin, 75-94.
Dugovic Branislav, Wagner Michael, Leumann Christian J. (2014), Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bcen-T and iso-tricyclo-T nucleosides, in Beilstein Journal of Organic Chemistry
, 10, 1840-1847.
Hollenstein Marcel, Leumann Christian J. (2014), Synthesis and Biochemical Characterization of Tricyclothymidine Triphosphate (tc-TTP), in ChemBioChem
, 15, 1901-1904.
Smith Christine C., Hollenstein Marcel, Leumann Christian J. (2014), The synthesis and application of a diazirine-modified uridine analogue for investigating RNA-protein interactions, in RSC Advances
, 4, 48228-48235.
Calabretta Alessandro, Leumann Christian J. (2013), Base Pairing and Miscoding Properties of 1,N6-Ethenoadenine- and 3,N4-Ethenocytosine-Containing RNA Oligonucleotides, in Biochemistry
, 52, 1990-1997.
Roethlisberger Pascal, Wojciechowski Filip, Leumann Christian J. (2013), Enhancement of Excess Electron Transfer Efficiency in DNA Containing a Phenothiazine Donor and Multiple Stable Phenanthrenyl Base Pairs, in Chemistry – A European Journal
, 19, 11518-11521.
Stucki SilvanR, Désiron Camille, Nyakas Adrien, Marti Simon, Leumann ChristianJ, Schürch Stefan (2013), Gas-phase Dissociation of homo-DNA Oligonucleotides, in Journal of the American Society for Mass Spectrometry
, 24, 1997-2006.
Stoop Matthias, Désiron Camille, Leumann Christian J. (2013), Nucleic acid sensing by an orthogonal reporter system based on homo-DNA, in Artificial DNA: PNA & XNA
, 4, 28-33.
Gerber Anna-Barbara, Leumann Christian J. (2013), Synthesis and Properties of Isobicyclo-DNA, in Chemistry – A European Journal
, 19, 6990-7006.
Wojciechowski Filip, Lietard Jory, Leumann Christian J. (2012), 2-Pyrenyl-DNA: Synthesis, Pairing, and Fluorescence Properties, in Organic Letters
, 14, 5176-5179.
Hollenstein Marcel, Wojciechowski Filip, Leumann Christian J. (2012), Polymerase incorporation of pyrene-nucleoside triphosphates, in Bioorganic & Medicinal Chemistry Letters
, 22, 4428-4430.
Tanaka M., Jaruga P., Kupfer P. A., Leumann C. J., Dizdaroglu M., Sonntag W. E., Chock P. B. (2012), RNA oxidation catalyzed by cytochrome c leads to its depurination and cross-linking, which may facilitate cytochrome c release from mitochondria, in Free Radical Biology and Medicine
, 53, 854-862.
Yaren Oezlem, Röthlisberger Pascal, Leumann C. J. (2012), Synthesis and Incorporation into Oligodeoxynucleotides of Carbocyclic, in Synthesis
, 44, 1011-1025.
Haziri Arben I., Leumann Christian J. (2012), Synthesis and Pairing Properties of Oligodeoxynucleotides Containing Bicyclo-RNA and Bicyclo-ANA Modifications, in Journal of Organic Chemistry
, 77, 5861-5869.
Lietard Jory, Leumann Christian J. (2012), Synthesis, Pairing, and Cellular Uptake Properties of C(6′)-Functionalized Tricyclo-DNA, in Journal of Organic Chemistry
, 77, 4566-4577.
Murray Sue, Ittig Damian, Koller Erich, Berdeja Andres, Chappell Alfred, Prakash Thazha P., Norrbom Michaela, Swayze Eric E., Leumann Christian J., Seth Punit P. (2012), TricycloDNA-modified oligo-2′-deoxyribonucleotides reduce scavenger receptor B1 mRNA in hepatic and extra-hepatic tissues—a comparative study of oligonucleotide length, design and chemistry, in Nucleic Acids Research
, 40, 6135-6143.
Yaren Oezlem, Mosimann Markus, Leumann Christian J. (2011), A Parallel Screen for the Discovery of Novel DNA Base Pairs, in Angew Chem Int Ed Engl
, 50, 1935-1938.
Wojciechowski Filip, Leumann Christian J. (2011), Alternative DNA base-pairs: from efforts to expand the genetic code to potential material applications, in Chemical Society Reviews
, 40, 5669-5679.
Tanaka M., Song H., Kupfer P. A., Leumann C. J., Sonntag W. E. (2011), An assay for RNA oxidation induced abasic sites using the Aldehyde Reactive ProbePosition-dependent effects on stability in tricyclo-DNA modified oligonucleotide duplexes, in Free Radical Research
, 45, 237-47.
Stoop Matthias, Leumann Christian J. (2011), Homo-DNA templated chemistry and its application to nucleic acid sensing, in Chemical Communications
, 47, 7494-7496.
Ittig D., Gerber A. B., Leumann C. J. (2011), Position-dependent effects on stability in tricyclo-DNA modified oligonucleotide duplexes, in Nucleic Acids Research
, 39, 373-80.
Tanaka Mikiei, Han Song, Küpfer Pascal A., Leumann Christian J., Sonntag William E. (2011), Quantification of oxidized levels of specific RNA species using an aldehyde reactive probe, in Analytical Biochemistry
, 417, 142-148.
Küpfer Pascal A., Leumann Christian J. (2011), Synthesis, base pairing properties and trans-lesion synthesis by reverse transcriptases of oligoribonucleotides containing the oxidatively damaged base 5-hydroxycytidine, in Nucleic Acids Research
, 39, 9422-9432.
Lietard Jory, Ittig Damian, Leumann Christian J. (2011), Synthesis, binding and cellular uptake properties of oligodeoxynucleotides containing cationic bicyclo-thymidine residues, in Bioorganic & Medicinal Chemistry
, 19, 5869-5875.
Tanaka Mikiei, Han Song, Kupfer Pascal A., Leumann Christian J., Chock Boon, Sonntag William E. (2010), Identification of Selectively Damaged mRNA in Response to Oxidative Stress: Characterization of Abasic sites using an Aldehyde Reactive Probe, in Free Radical Biology and Medicine
, 49, 172-172.
Ittig D., Luisier S., Weiler J., Schümperli D., Leumann C. (2010), Improving gene silencing of siRNAs via tricyclo-DNA modification, in Artificial DNA: PNA & XNA
, 1, 9-16.
Silhár Peter, Leumann Christian J. (2010), Parallel synthesis and nucleic acid binding properties of C(6')-[alpha]-functionalized bicyclo-DNA, in Bioorganic & Medicinal Chemistry
, 18, 7786-7793.
Luisier S., Leumann C. J. (2010), Screening the structural space of bicyclo-DNA: synthesis and properties of bicyclo-DNA functionalized at C(6'), in Heterocycles
, 82, 775-790.
Haziri A. I., Silhar P., Renneberg D., Leumann C. J. (2010), Synthesis of the Sugar Building Block of Bicyclo-RNA, in Synthesis
This NF-grant application contains four separate sub-projects that all deal with the design, synthesis and the evaluation of novel, chemically modified oligonucleotide analogues. These analogues are of interest for DNA therapy, for DNA based diagnostics, as molecular architectures for DNA based functional materials or as tools to follow cellular metabolism.The first sub-project deals with the synthesis of novel nucleosides and oligonucleotides of the bicyclo-DNA family with the aim of improving RNA affinity and cellular uptake and distribution. Molecular modeling has been used as a designer tool to improve RNA affinity. The pro-drug concept has been applied to enhance membrane permeability.The second sub-project is devoted to the optimization of our recently discovered phenanthrene DNA-zipper recognition motif. Also here, molecular dynamics on a QM/MM level will be used for identifying the best geometries of differently attached phenanthrene units in the base stack and for predicting the ionization potentials of differently substituted phenanthrene units. Further experiments are devoted to the structural characterization of multiply substituted duplexes by X-ray crystallography and to the investigation of the charge transport properties through the phenanthrene units by using nanoelectrochemical methods. The ultimate goal here is to construct an efficient charge separating device based on this novel DNA architecture.Another sub-project is concerned with the biological impact of damaged RNA. Having in hand a powerful method for the synthesis of abasic RNA we want now to investigate the fate of such RNA lesions during translation at the ribosome. In addition we will synthesize RNA with the oxidatively damaged bases 5-hydroxyuracil and 5-hydroxycytosine and investigate their impact on transcription and translation. The results of this sub-project will increase our general understanding of the biological impact of such RNA lesions that can occur naturally.The final sub-project aims at improving the selectivity and sensitivity of current RNA or DNA detection systems by using hybrid DNA/homo-DNA probes. This system is based on a homo-DNA templated Staudinger reaction, converting a covalently attached non-fluorescent to a fluorescent dye upon RNA target recognition. This system is designed towards catalytic signal enhancement and should thus lead to high sensitivity probes allowing the detection of low abundance RNA probes. In addition the use of a bioorthogonal base-pairing system (homo-DNA) and a bioorthogonal chemical reaction (Staudinger reaction) is expected to lead to less false positive signals and may show improved in vivo performance.