Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 7 uppsatser.

by Chiu Wing Lok Abe Kurtz. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 218-230). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Ip Lai Nang. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 67-71). / Abstracts in English and Chinese. / ABSTRACT (ENGLISH) --- p.iii / ABSTRACT (CHINESE) --- p.iv / ACKNOWLEDGEMENTS --- p.v / TABLE OF CONTENTS --- p.vi / LIST OF TABLES --- p.viii / LIST OF FIGURES --- p.ix / LIST OF APPENDIX --- p.x / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter CHAPTER 2 --- BACKGROUND --- p.3 / Chapter 2.1 --- Structure of DNA --- p.3 / Chapter 2.2 --- Sequence dependent stability --- p.8 / Chapter 2.3 --- Thermodynamics of DNA --- p.9 / Chapter 2.4 --- Model for predicting thermodynamic parameters of DNA sequence --- p.15 / Chapter 2.4.1 --- The nearest-neighbor (NN) model / Chapter 2.4.1.1 --- Background --- p.15 / Chapter 2.4.1.2 --- Method for predicting thermodynamic parameters --- p.16 / Chapter 2.4.1.3 --- Limitation of the NN model --- p.19 / Chapter CHAPTER 3 --- EXPERIMENTAL METHOD --- p.20 / Chapter 3.1 --- Design of DNA sequences PAGE --- p.20 / Chapter 3.2 --- DNA synthesis and purification --- p.22 / Chapter 3.3 --- UV measurement --- p.23 / Chapter CHAPTER 4 --- THE NEXT NEAREST-NEIGHBOR (NNN) MODEL --- p.27 / Chapter 4.1 --- Method for extracting the NNN thermodynamic parameters --- p.30 / Chapter 4.2 --- Discussions --- p.34 / Chapter 4.2.1 --- Comparison of the NN model and the NNN model --- p.34 / Chapter 4.2.2 --- The NNN effect --- p.38 / Chapter 4.2.3 --- Sequence-specific local structure of DNA and the NNN effect / Chapter CHAPTER 5 --- SUMMARY AND FUTURE WORK --- p.49 / APPENDIX I´ؤ XVI --- p.51 / REFERENCE --- p.67

Fenn, Dickson. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 74-81). / Abstract also in Chinese. / Title Page --- p.i / Thesis Committee --- p.ii / Acknowledgement --- p.iii / Table of Contents --- p.v / List of Tables --- p.ix / List of Figures --- p.x / List of Abbreviations and Symbols --- p.xv / Abstract --- p.xvii / Chapter 1.Chapter One: --- Introduction --- p.1 / Chapter 1.1 --- Oxidation and Hyperoxidation of Guanine --- p.1 / Chapter 1.2. --- DNA Replication --- p.2 / Chapter 1.3 --- Mutagenesis --- p.3 / Chapter 1.4 --- Literature Survey on Spiroiminodihydantoin (Sp) --- p.4 / Chapter 1.5 --- Purpose of This Work --- p.5 / Chapter 1.6 --- DNA Structure --- p.6 / Chapter 1.6.1 --- Nomenclature --- p.6 / Chapter 1.6.2 --- Torsion Angles --- p.6 / Chapter 1.6.3 --- Sugar Pucker Conformation --- p.7 / Chapter 1.6.4 --- Secondary Structures of DNA --- p.8 / Chapter 2.Chapter Two: --- Materials and Methodology --- p.10 / Chapter 2.1 --- Sample Design --- p.10 / Chapter 2.2 --- Sample Preparation --- p.11 / Chapter 2.2.1 --- DNA Synthesis and Purification --- p.11 / Chapter 2.2.2 --- HPLC Separation --- p.11 / Chapter 2.2.3 --- NMR Samples Preparation --- p.12 / Chapter 2.3 --- NMR Analysis --- p.12 / Chapter 2.3.1 --- Resonance Assignment --- p.14 / Chapter 2.3.1.1 --- Proton --- p.14 / Chapter 2.3.1.2 --- Phosphorous --- p.16 / Chapter 2.3.2 --- Sugar Pucker Conformation --- p.17 / Chapter 2.3.3 --- Backbone Conformation --- p.18 / Chapter 2.4 --- UV Melting Analysis --- p.19 / Chapter 3.Chapter Three: --- "HPLC, NMR and UV Results" --- p.21 / Chapter 3.1 --- HPLC Separation of Sp Diastereoisomers --- p.21 / Chapter 3.2 --- NMR Resonance Assignments --- p.24 / Chapter 3.2.1 --- 5'-GG Sample --- p.24 / Chapter 3.2.2 --- 5'-G(oG) Sample --- p.26 / Chapter 3.2.3 --- 5'-G(Sp) Sample --- p.29 / Chapter 3.2.4 --- 5'-T(oG) Sample --- p.31 / Chapter 3.2.5 --- 5'-T(Sp) Sample --- p.34 / Chapter 3.3 --- Sugar Pucker Conformation --- p.38 / Chapter 3.4 --- Backbone Conformation --- p.41 / Chapter 3.5 --- UV Melting --- p.43 / Chapter 4.Chapter Four: --- Effect of Spiroiminodihydantoin and 7-hydro-8-oxoguanine on Primer-Template Structures --- p.44 / Chapter 4.1 --- Overview --- p.42 / Chapter 4.2 --- NMR Investigations of the Primer-Template Models --- p.45 / Chapter 4.2.1 --- Incorporation of a dCTP Opposite a 5'-GG Template --- p.45 / Chapter 4.2.2 --- Incorporation of a dCTP Opposite a 5'-G(oG) Template --- p.46 / Chapter 4.2.3 --- Incorporation of a dCTP Opposite a 5'-G(Sp) Template --- p.48 / Chapter 4.2.4 --- Incorporation of a dATP Opposite a 5'-T(oG) Template --- p.50 / Chapter 4.2.5 --- Incorporation of a dATP Opposite a 5'-T(Sp) Template --- p.51 / Chapter 4.3 --- Effect of Sp and oG on Primer-Template Structures --- p.52 / Chapter 4.3.1 --- Misaligned Structure with a Sp-Bulge --- p.52 / Chapter 4.3.2 --- C·oG Base Pair in 5'-G(oG) --- p.54 / Chapter 4.3.3 --- Biological Implications --- p.54 / Chapter 5. --- Chapter Five: Preliminary Structural Calculations on Primer- Template Structures --- p.56 / Chapter 5.1 --- Experimental Restraints Extraction --- p.56 / Chapter 5.2 --- Experimental Restraints Distribution --- p.58 / Chapter 5.3 --- Structural Calculations --- p.60 / Chapter 5.4 --- Structural Results --- p.62 / Chapter 5.4.1 --- 5'-GG --- p.63 / Chapter 5.4.2 --- 5'-G(oG) --- p.64 / Chapter 5.4.3 --- 5'-T(oG) --- p.65 / Chapter 5.4.4 --- 5'-T(SpR) with 5'-T(Spl) Restraints --- p.66 / Chapter 5.4.5 --- 5'-T(SpR) with 5'-T(Sp2) Restraints --- p.67 / Chapter 5.4.6 --- 5'-T(SpS) with 5'-T(Spl) Restraints --- p.68 / Chapter 5.4.7 --- 5'-T(SpS) with 5'-T(Sp2) Restraints --- p.69 / Chapter 5.6 --- Structural Analysis --- p.70 / Chapter 6. --- Chapter Six: Conclusions and Future Work --- p.72 / Appendix --- p.73 / References --- p.74

Yang, Hao. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 53-57). / Abstract also in Chinese. / Title Page --- p.i / Thesis Committee --- p.ii / Abstract (English version) --- p.iv / Abstract (Chinese version) --- p.vi / Acknowledgment --- p.vii / Table of Contents --- p.viii / List of Tables --- p.xi / List of Figures --- p.xii / List of Abbreviations and Symbols --- p.xv / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- DNA Methylation --- p.1 / Chapter 1.2 --- DNA Methylation Repair --- p.2 / Chapter 1.3 --- Objectives of This Work --- p.2 / Chapter 1.4 --- DNA Structure --- p.3 / Chapter 1.4.1 --- Nomenclature Scheme for DNA --- p.3 / Chapter 1.4.2 --- Base Pair Scheme --- p.4 / Chapter 1.4.3 --- Sugar Conformation --- p.5 / Chapter 1.4.4 --- Backbone Conformation --- p.5 / Chapter 2 --- Materials and Methods --- p.7 / Chapter 2.1 --- Sample Design --- p.7 / Chapter 2.2 --- Sample Preparation --- p.7 / Chapter 2.3 --- UV Optical Melting Study --- p.8 / Chapter 2.4 --- NMR Study --- p.9 / Chapter 2.4.1 --- NMR Melting Study --- p.10 / Chapter 2.4.2 --- Resonance Assignment --- p.10 / Chapter 2.4.3 --- Determination of Sugar Conformation --- p.12 / Chapter 2.4.4 --- Determination of Backbone Conformation --- p.13 / Chapter 3 --- Effect of 1-Methyladenine on Double-Helical DNA Structures --- p.14 / Chapter 3.1 --- NMR Resonance Assignments --- p.14 / Chapter 3.1.1 --- TA-oligo Resonance Assignments --- p.14 / Chapter 3.1.2 --- TmlA-oligo Resonance Assignments --- p.16 / Chapter 3.2 --- DNA Double-Helical Structures upon 1-Methylation of Adenine --- p.18 / Chapter 3.2.1 --- Base Pairing Mode --- p.18 / Chapter 3.2.2 --- Sugar Puker --- p.21 / Chapter 3.2.3 --- Backbone Conformation --- p.22 / Chapter 3.3 --- Summary --- p.24 / Chapter 4 --- Effect of 1-Methyladenine on Double-Helical DNA Stabilities --- p.25 / Chapter 4.1 --- Thermodynamic Studies --- p.26 / Chapter 4.1.1 --- Influence of m6A on UV Melting Studies --- p.26 / Chapter 4.1.2 --- Thermodynamics by NMR Melting Studies --- p.28 / Chapter 4.2 --- "NMR Structural Studies on Gm1A-, Am1A- and Cm1A-oligo" --- p.33 / Chapter 4.2.1 --- Gml A-oligo --- p.33 / Chapter 4.2.1.1 --- Gm1A-oligo Resonance Assignments --- p.33 / Chapter 4.2.1.2 --- Base Pair Structures of Gm1A-oligo --- p.35 / Chapter 4.2.2 --- AmiA-oligo --- p.37 / Chapter 4.2.2.1 --- Am1A-oligo Resonance Assignments --- p.37 / Chapter 4.2.2.2 --- Base Pair Structures of Am1A-oligo --- p.39 / Chapter 4.2.3 --- Cm1A-oligo --- p.43 / Chapter 4.2.3.1 --- Cm1A-oligo Resonance Assignments --- p.43 / Chapter 4.2.3.2 --- Base Pair Structures of Cm1A-oligo --- p.45 / Chapter 4.3 --- Summary --- p.46 / Chapter 5 --- Conclusion and Future work --- p.47 / Appendix I Proton chemical shift values of TA-oligo --- p.48 / Appendix II Proton chemical shift values of TmlA-oligo --- p.49 / Appendix III Proton chemical shift values of GmlA-oligo --- p.50 / Appendix IV Proton chemical shift values of Am1A-oligo --- p.51 / Appendix V Proton chemical shift values of CmlA-oligo --- p.52 / References --- p.53

Oligonucleotides are short fragments of DNA (10-100nt) which are of great interest because their applications in molecular biology, biomedicine and nanotechnology. As a result of their ability to base pairing, oligonucleotides can be used as primers, hybridization probes in biosensors, agents for controlling gene expression, structural material in nanotechnology or as substrates for a variety of biochemical and biophysical studies. Chemical modification of oligonucleotides as well as conjugation to different functional molecules allows for modulation of both therapeutical and biotechnological properties. This thesis is focused in the nucleic acid chemistry field and the main objective is the synthesis of modified oligonucleotides for obtaining structures with therapeutical and/or biotechnological interest. Oligonucleotides capable to form structures other than the canonical DNA double helix have received considerable attention in the last years. The ability of triplex forming oligonucleotides (TFOs) to bind specifically to certain duplex DNA regions provides a strategy for site-directed modification of genomic DNA. Besides, G-quadruplexes are four-stranded DNA structures stabilized by stacking of guanine tetrads which have been found in telomeres and some promoters and play a role in regulation of transcription and translation. In addition, they are also interesting for nanotechnological devices. In this context, the first part of the research work was addressed to synthesize parallel stranded oligonucleotide clamps carrying LNA (locked nucleic acid) residues and study the stability of the triplex formed with DNA and RNA target sequences. Secondly, a novel strategy to obtain parallel clamps using the non-templated chemical ligation of two oligonucleotides by 5’-5’ linkages was developed. For this purpose, several protocols for introduce azido and alkyne moieties in the 5’-end of different sequences were developed so that the modified DNA strands could form a parallel hairpin after their chemical ligation by click chemistry. Thirdly, a system composed of four DNA strands whose 5’ ends are covalently attached was designed to form a monomolecular parallel G-quadruplex, which was used to study the effects of some nucleobase modifications in quadruplex structure. Finally, oligonucleotide conjugates carrying Cu(II) complexes were synthesized to construct arrays of electrochemical oscillators for nanotechnology applications.

Yes / Curiouser and curiouser! A biarylpyrimidine ligand (see picture: N blue, H cyan, S yellow) shows a marked structure and sequence selectivity for the poly(dA)⋅poly(rU) hybrid duplex. An intercalative binding site was discovered where the ligand occupies a surprising ten base pairs. A strong correlation between hybrid duplex and DNA triplex binding indicates new directions for ligand design.