Sökning: "azetidine"

Visar resultat 1 - 5 av 6 avhandlingar innehållade ordet azetidine.

1. 1. 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

3. 2. 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

4. 3. 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

5. 4. Physicochemical and Structural Aspects of Nucleic Acids

   Författare :Subhrangsu Chatterjee; Adolf Gogoll; Helena Grennberg; Göran Widmalm; Uppsala universitet; []
   Nyckelord :NATURVETENSKAP; NATURAL SCIENCES; Organic chemistry; pKa; Hydrogen bonding; Stacking; NMR; MD; DNA; RNA; Pyrimidine; Organisk kemi;

   Sammanfattning : This thesis consists of seven research publications concerning (i) pKa studies of nucleobases in model nucleotides to understand why RNA duplexes are more stable than DNA duplexes (Paper I), (ii) the role of Me(T)-π interactions in the relative stability of DNA-RNA heteroduplexes (Paper II), (iii) pKa measurements in nucleotides with different 2′-substituents (paper III), (iv) a conformation study of constrained sugars and a pKa study of 1-thyminyl to reveal effect of sugar constraints on the pKa of the nucleobase (paper IV), (v) NMR and MD studies of 1′, 2′-oxetane constrained thymidine incorporated Dickerson Drew dodecamer (paper V), (vi) the sequence dependent pKa perturbation of 9-guaninyl moeity in single stranded (ss) DNA and RNA (paper VI), (vii) the non identical chemical nature of internucleotidic phosphates in (ss) RNA using 31P NMR (paper VI), and an alkaline hydrolysis study of phosphodiesters in ssRNAs (paper VII). The architecture of DNA and RNA molecules is determined by (a) hydrogen bonding (b) base stacking (c) a variety of additional non-covalent interactions. LÄS MER

7. 5. Structural and Biophysical Studies of Nucleic Acids

   Författare :Wimal Pathmasiri; Adolf Gogoll; Lena Mäler; Uppsala universitet; []
   Nyckelord :Organic chemistry; nucleic acids; Nuclear Magnetic Resonance; molecular dynamics; sugar modified nucleosides; pKa; Organisk kemi;

   Sammanfattning : This thesis is based on six research publications concerned with (i) study of the molecular structures and dynamics of modified nucleosides; (ii) investigation of the effect of incorporation of modified nucleosides on the structure of DNA; (iii) examination of the effect of the sugar modifications on the pseudo-aromatic properties (pKa) of the nucleobases; (iv) analysis of the effect of the CH-π interactions on the relative stability of the DNA-RNA hybrid duplexes. The structural stability of the nucleic acids as well as their behavior in molecular recognition is dominated by hydrogen bonding and stacking interactions beside other non-covalent interactions. LÄS MER