Sökning: "RNase H cleavage"

Visar resultat 1 - 5 av 12 avhandlingar innehållade orden RNase H cleavage.

  1. 1. Targeting RNA by the Antisense Approach and a Close Look at RNA Cleavage Reaction

    Författare :Jharna Barman; Lars Baltzer; Roger Strömberg; Uppsala universitet; []
    Nyckelord :NATURVETENSKAP; NATURAL SCIENCES; Organic chemistry; mRNA targeting; antisense oligonucleotides; target affinity; RNase H; Michaelis-Menten kinetics; exo-nuclease stability; NMR; pH titration; alkaline hydrolysis; Organisk kemi;

    Sammanfattning : This thesis summarizes the results of studies on two aspects of nucleic acids. Chemically modified antisense oligonucleotides (AONs) have been evaluated with regards to their suitability for mRNA targeting in an antisense approach (Paper I – III). LÄS MER

  2. 2. Aspects of Antisense and Antigene Chemistry of Oligonucleotides Tethered to Intercalators

    Författare :Dimitri Ossipov; Jesper Wengel; Uppsala universitet; []
    Nyckelord :NATURVETENSKAP; NATURAL SCIENCES; Bioorganic chemistry; oligonucleotides; intercalators; ruthenium complexes; RNase H cleavage; photocross-linkage; Bioorganisk kemi; Bioorganic chemistry; Bioorganisk kemi; bioorganisk kemi; Biorganic Chemistry;

    Sammanfattning : Synthetic and physicochemical studies on appropriately functionalized ODN-conjugates have been performed to evaluate their abilities to act as antisense agents against RNA or as intramolecular DNA cross-linking agents. Intercalating aromatic systems [phenazine (Pnz), dipyridophenazine (DPPZ)] and metallointercalators such as Ru2+(phen)2(DPPZ) and Ru2+(tpy)(DPPZ)L [where L = chemically or photochemically labile ligand, phen = phenanthroline, tpy = terpyridine], which are covalently tethered to the oligo-deoxynucleotides (ODNs), have been chosen for this purpose. LÄS MER

  3. 3. Chemically Modified Oligonucleotides: Synthesis, Physicochemical and Biochemical Properties of their Duplexes with DNA and RNA

    Författare :Pushpangadan Indira Pradeepkumar; Jyoti Chattopadhyaya; Jesper Wengel; Uppsala universitet; []
    Nyckelord :NATURVETENSKAP; NATURAL SCIENCES; Bioorganic chemistry; Antisense oligonucleotides; Dipyridophenazine; Oxetane; RNase H; Gene down-regulation; DNase 1; Charge transport; Bioorganisk kemi; Bioorganic chemistry; Bioorganisk kemi;

    Sammanfattning : This thesis is based on 9 papers dealing with the synthesis, physicochemical and biochemical properties of two types of chemically modified oligonucleotides which have the potential to down-regulate gene expression: (i) The first set is comprised of antisense oligonucleotides (AONs) conjugated with different chromophores of varying size, charge and π-electron density. Conjugation of the chromophores at the 3'- or 5'-end enhanced the target RNA binding affinity and RNase H recruitment capabilities compared to the native counterpart without changing the global helical conformation of their AON/RNA hybrid duplexes. LÄS MER

  4. 4. Conformationally Constrained Nucleosides, Nucleotides and Oligonucleotides : Design, Synthesis and Properties

    Författare :Dmytro Honcharenko; Jyoti Chattopadhyaya; Piet Herdewijn; Uppsala universitet; []
    Nyckelord :NATURVETENSKAP; NATURAL SCIENCES; Bioorganic chemistry; antisense oligonucleotides; conformationally constrained nucleosides; azetidine; aza-ENA; target affinity; RNase H; exonuclease stability; pyrene-functionalized nucleotides; fluorescence; mismatch discrimination; Bioorganisk kemi; Cell and molecular biology; Cell- och molekylärbiologi;

    Sammanfattning : This thesis is based on six original research publications describing synthesis, structure and physicochemical and biochemical analysis of chemically modified oligonucleotides (ONs) in terms of their potential diagnostic and therapeutic applications. Synthesis of two types of bicyclic conformationally constrained nucleosides, North-East locked 1',2'-azetidine and North locked 2',4'-aza-ENA, is described. LÄS MER

  5. 5. Conformationally Constrained Oligonucleotides for RNA Targeting

    Författare :Qing Li; Jyoti Chattopadhyaya; Li-He Zhang; Uppsala universitet; []
    Nyckelord :NATURVETENSKAP; NATURAL SCIENCES; NATURVETENSKAP; NATURAL SCIENCES; conformationally constrained nucleoside; antisense oligonucleotide; RNA affinity; nuclease stability; RNase H; RNA degradation; Chemistry with specialization in Bioorganic Chemistry; Kemi med inriktning mot bioorganisk kemi;

    Sammanfattning : A short oligonucleotide sequence as in a single-stranded antisense oligo nucleotides (AON) or in double-stranded small interfering RNAs (siRNA) can modulate the gene expression by targeting against the cellular mRNA, which can be potentially exploited for therapeutic purposes in the treatment of different diseases. In order to improve the efficacy of oligonucleotide-based drugs, the problem of target affinity, nuclease stability and delivery needs to be addressed. LÄS MER