Sökning: "chemically modified oligonucleotides"

Visar resultat 1 - 5 av 11 avhandlingar innehållade orden chemically modified oligonucleotides.

1. 1. Conformationally Constrained Nucleosides : Design, Synthesis, and Biochemical Evaluation of Modified Antisense Oligonucleotides

   Författare :Oommen P. Varghese; Lars Engman; Jacek Stawinski; Uppsala universitet; []
   Nyckelord :NATURVETENSKAP; NATURAL SCIENCES; Organic chemistry; chemically modified oligonucleotides; azetidine; aza-ENA-T; cyanomethylene locked; free energy of activation; diaxial interactions; chair conformation; stable duplex; human serum; snake venom phosphodiesterase; antisense agents; RNase H; Organisk kemi; Chemistry; Kemi;

   Sammanfattning : This thesis is concerned with synthesis, structure and biochemical analysis of chemically modified oligonucleotides with potential therapeutic applications. The three types of chemical modifications described here are: (a) A North-East locked 1',2'-azetidine nucleoside (b) A North locked 2',4'-cyanomethylene bridged nucleoside and (c) A 2',4'-aza-ENA-T nucleoside. LÄS MER

3. 2. Cell-penetrating peptides and oligonucleotides : Design, uptake and therapeutic applications

   Författare :Andrés Muñoz-Alarcón; Ülo Langel; Sandrine Sagan; Stockholms universitet; []
   Nyckelord :NATURVETENSKAP; NATURAL SCIENCES; Cell-penetrating peptides; oligonucleotides; scavenger receptors; telomerase; gene therapy; neurokemi med molekylär neurobiologi; Neurochemistry with Molecular Neurobiology;

   Sammanfattning : Regulation of biological processes through the use of genetic elements is a central part of biological research and also holds great promise for future therapeutic applications. Oligonucleotides comprise a class of versatile biomolecules capable of modulating gene regulation. LÄS MER

4. 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

5. 4. 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

7. 5. 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