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Chemistry and Biology of Non-canonical Nucleic Acids. Edition No. 1

  • Book

  • 288 Pages
  • April 2021
  • John Wiley and Sons Ltd
  • ID: 5837951
Discover the fundamentals and intricacies of a subject at the interface of chemistry and biology with this authoritative resource

Chemistry and Biology of Non-canonical Nucleic Acids delivers a comprehensive treatment of the chemistry and biology of non-canonical nucleic acids, including their history, structures, stabilities, properties, and functions. You'll learn about the role of these vital compounds in transcription, translation, regulation, telomeres, helicases, cancers, neurodegenerative diseases, therapeutic applications, nanotechnology, and more.

An ideal resource for graduate students, researchers in physical, organic, analytical, and inorganic chemistry will learn about uncommon nucleic acids, become the common non-canonical nucleic acids that fascinate and engage academics and professionals in private industry.

Split into 15 chapters covering a wide range of aspects of non-canonical nucleic acids, the book explains why these compounds exist at the forefront of a new research revolution at the intersection of chemistry and biology. Chemistry and Biology of Non-canonical Nucleic Acids also covers a broad range of topics critical to understanding these versatile and omnipresent chemicals, including:

A discussion of the dynamic regulation of biosystems by nucleic acids with non-canonical structures
The role played by nucleic acid structures in neurodegenerative diseases and various cancers
An exploration of the future outlook for the chemistry and biology of non-canonical nucleic acids
An introduction to the history of canonical and non-canonical structures of nucleic acids
An analysis of the physicochemical properties of non-canonical nucleic acids

Perfect for biochemists, materials scientists, and bioengineers, Chemistry and Biology of Non-canonical Nucleic Acids will also earn a place in the libraries of medicinal and pharmaceutical chemists who wish to improve their understanding of life processes and the role that non-canonical nucleic acids play in them.

Table of Contents

Preface xi

1 History for Canonical and Non-canonical Structures of Nucleic Acids 1

1.1 Introduction 1

1.2 History of Duplex 1

1.3 Non-Watson-Crick Base Pair 5

1.4 Nucleic Acid Structures Including Non-Watson-Crick Base Pairs 7

1.5 Perspective of the Research for Non-canonical Nucleic Acid Structures 8

1.6 Conclusion and Perspective 9

References 9

2 Structures of Nucleic Acids Now 11

2.1 Introduction 11

2.2 Unusual Base Pairs in a Duplex 11

2.2.1 Hoogsteen Base Pair 13

2.2.2 Purine-Pyrimidine Mismatches 13

2.2.3 Purine-Purine Mismatches 14

2.2.4 Pyrimidine-Pyrimidine Mismatches 16

2.3 Non-canonical Backbone Shapes in DNA Duplex 17

2.4 Branched DNA with Junction 19

2.5 Multi-stranded DNA Helices 20

2.6 Structures in RNA 20

2.6.1 Basic Structure Distinctions of RNA 20

2.6.2 Elements in RNA Secondary Structures 21

2.6.2.1 Hairpin Loop 22

2.6.2.2 Bulge Loop 22

2.6.2.3 Internal Loop 23

2.6.3 Elements in Tertiary Interactions of RNA 24

2.6.3.1 A-Minor Interactions 25

2.6.3.2 Ribose Zipper 25

2.6.3.3 T-Loop Motif 26

2.6.3.4 Kissing-Loop Interaction 26

2.6.3.5 GNRA Tetraloop Receptor Interaction 27

2.6.3.6 Pseudoknot Crosslinking Distant Stem Regions 29

2.7 Conclusion 29

References 30

3 Stability of Non-canonical Nucleic Acids 33

3.1 Introduction 33

3.2 Factors Influencing Stabilities of the Canonical Duplexes 34

3.2.1 Hydrogen Bond Formations 34

3.2.2 Stacking Interactions 35

3.2.3 Conformational Entropy 35

3.3 Thermodynamic Analysis for the Formation of Duplex 36

3.4 Factors Influencing Stabilities of the Non-canonical Nucleic Acids 39

3.4.1 Factors Influencing Stability of Triplexes 39

3.4.2 Factors Influencing Stability of Quadruplex 42

3.4.2.1 G-Quadruplexes 42

3.4.2.2 i-Motif 44

3.5 Thermodynamic Analysis for the Non-canonical Nucleic Acids 45

3.5.1 Thermodynamic Analysis for the Intramolecular Triplex and Tetraplex 45

3.5.2 Thermodynamic Analysis for the Intermolecular Triplex 45

3.5.3 Thermodynamic Analysis for the Tetraplex 46

3.6 Conclusion 48

References 49

4 Physicochemical Properties of Non-canonical Nucleic Acids 51

4.1 Introduction 51

4.2 Spectroscopic Properties of Non-canonical Nucleic Acids 51

4.2.1 Effect of Non-canonical Structure on UV Absorption 51

4.2.2 Circular Dichroism of Non-canonical Nucleic Acids 53

4.2.3 NMR Spectroscopy 56

4.2.4 Other Spectroscopic Characteristics of Non-canonical Nucleic Acids 57

4.3 Chemical Interactions on Non-canonical Nucleic Acids 59

4.3.1 Hydration 59

4.3.2 Cation Binding 61

4.3.3 pH Effect 62

4.3.4 Chemical Modification 63

4.4 Chemical Platform on the Non-canonical Structures 64

4.4.1 Specificity of a Ligand to Non-canonical Structures 64

4.4.2 Fluorescence Platform of Non-canonical Structures 67

4.4.3 Interface Between Proteins and Nucleic Acids 68

4.5 Physicochemical Property of Non-canonical Nucleic Acids in Cell 69

4.5.1 Molecular Crowding Condition that Reflects Cellular Environments 69

4.5.2 Effects of Crowding Reagents on Non-canonical Nucleic Acid Structures 70

4.5.3 Quantification of Physical Properties of Non-canonical Structures in Crowding Condition 71

4.5.4 Non-canonical Structures Under Mimicking Organelle Environment 72

4.5.5 Insight for the Formation of Non-canonical Nucleic Acids in Cells 73

4.6 Conclusion 75

References 75

5 Telomere 79

5.1 Introduction 79

5.2 Structural Properties of Telomere 79

5.2.1 Structures of Telomere 79

5.2.2 Structural Properties of Human Telomeric G4s 81

5.2.3 Structure of Repeats of Human Telomeric G4s 84

5.3 Biological Relevance of Telomere G4 86

5.3.1 Telomerase Activity 86

5.3.2 Telomerase Repeated Amplification Protocol (TRAP) Assay 89

5.3.3 Alternative Lengthening of Telomere (ALT) Mechanism 89

5.4 Other Non-canonical Structures Related to Telomere Region 89

5.4.1 Telomere i-Motif 89

5.4.2 Telomere RNA 90

5.5 Conclusion 92

References 93

6 Transcription 95

6.1 Introduction 95

6.2 Transcription Process 96

6.2.1 Transcription Initiation 96

6.2.2 Transcription Elongation 98

6.2.3 Transcription Termination 99

6.3 Transcription Process Perturbed by Certain Sequences of DNA and RNA 101

6.4 Transcription Process Perturbed by Non-canonical Structures of DNA and RNA 103

6.5 Conclusion 110

References 110

7 Translation 113

7.1 Introduction 113

7.2 RNAs Involved in Translation Machinery 113

7.3 General Process of Translation 117

7.3.1 Translation Initiation 117

7.3.2 Translation Elongation 119

7.3.3 Translation Termination 119

7.4 RNA Structures Affecting Translation Reaction 121

7.4.1 Modulation of Translation Initiation in Prokaryotes 121

7.4.2 Modulation of Translation Initiation in Eukaryotes 123

7.4.3 RNA Structures Affecting Translation Elongation 126

7.4.4 RNA Structures Affecting Translation Termination 130

7.5 Conclusion 133

References 134

8 Replication 137

8.1 Introduction 137

8.2 Replication Machineries 137

8.3 Replication Initiation 138

8.3.1 Mechanism of Activation of Replication Origins 138

8.3.2 Activation Control of Origins by G4s 139

8.3.3 Control of Timing of Replication Initiation by G4s 142

8.4 DNA Strand Elongation 142

8.4.1 Mechanism of DNA Strand Elongation 142

8.4.2 Impact of G4 and i-Motif Formations on DNA Strand Synthesis 144

8.4.3 Relationship Between G4 and Epigenetic Modification 145

8.4.4 Expansion and Contraction of Replicating Strand Induced by Hairpin Structures 147

8.5 Termination of Replication 148

8.6 Chemistry of the Replication and Its Regulation 148

8.6.1 Cellular Environments 148

8.6.2 Control of Replication by Chemical Compounds 150

8.7 Conclusion 151

References 152

9 Helicase 155

9.1 Introduction 155

9.2 Function and Structure of Helicases 155

9.3 Unwinding of Non-canonical DNA Structures by Helicases 158

9.4 G4 Helicases in Gene Expressions 162

9.5 G4 Helicases in Replication 163

9.6 G4 Helicases in Telomere Maintenance 164

9.7 Relation to Diseases by Loss of G4 Helicases 165

9.8 Insight into Specific Properties of Activities of G4 Helicase Under Cellular Conditions 165

9.9 Conclusion 167

References 167

10 Dynamic Regulation of Biosystems by Nucleic Acids with Non-canonical Structures 171

10.1 Introduction 171

10.2 Time Scale of Biological Reactions 171

10.2.1 Cell Cycle 172

10.2.2 Central Dogma 172

10.2.3 Dynamic Structures of Nucleic Acids 174

10.3 Processes in the Central Dogma Affected by Dynamics of Nucleic Acid Structures 176

10.3.1 Epigenetic Regulation Caused by Chemical Modification of DNA 176

10.3.2 Co-transcriptional Formation of Metastable RNA Structures 178

10.3.3 Co-transcriptional Translation and Transcription Attenuation 180

10.3.4 Co-transcriptional Ligand Binding and Gene Regulation 181

10.3.5 Translation Elongation and Co-translational Protein Folding 183

10.4 Conclusion 184

References 185

11 Cancer and Nucleic Acid Structures 189

11.1 Introduction 189

11.2 Detail Mechanism of Cancer 189

11.2.1 Cancer Incidence 189

11.2.2 The Relationship Between Genes and Cancer 192

11.3 Non-canonical Structures of Nucleic Acids in Cancer Cells 192

11.3.1 Structural Characteristics of Nucleic Acids in Cancer Cells 192

11.3.2 Non-canonical Structures Perturb Gene Expression of Cancer-Related Genes 195

11.4 Roles of Non-canonical Structures of Nucleic Acids in Cancer Cells 197

11.4.1 Monitoring of Non-canonical Structures in Cancer Cells 197

11.4.2 Regulation of Gene Expressions by the Non-canonical Structures in Cancer Cells 198

11.5 Conclusion 199

References 199

12 Neurodegenerative Diseases and Nucleic Acid Structures 203

12.1 Introduction 203

12.2 Protein Aggregation-Induced Neurodegenerative Diseases 203

12.3 DNA Shows Key Role for Neurodegenerative Diseases 205

12.4 RNA Toxic Plays a Key Role for Neurological Diseases 210

12.5 Conclusion 212

References 212

13 Therapeutic Applications 215

13.1 Introduction 215

13.2 Oligonucleotide Therapeutics 216

13.2.1 Antisense Oligonucleotide 216

13.2.2 Functions of Antisense Oligonucleotide Therapeutics 217

13.2.3 Chemical Modifications in Therapeutic Oligonucleotides 220

13.2.3.1 Backbone Modified Oligonucleotides 220

13.2.3.2 Ribose Modified Oligonucleotides 221

13.2.3.3 Oligonucleotides with Unnatural Backbone 221

13.2.4 Oligonucleotide Therapeutics Other Than Antisense Oligonucleotide 223

13.2.4.1 Oligonucleotide Therapeutics Functioning Through RNA Interference 224

13.2.4.2 Oligonucleotide Therapeutics Functioning Through Binding to Protein 224

13.3 Non-canonical Nucleic Acid Structures as Therapeutic Targets 224

13.3.1 Traditional Antibiotics Targeting Structured Region of RNAs 225

13.3.2 Strategies for Constructing Therapeutic Materials Targeting Structured Nucleic Acids 226

13.4 Non-canonical Nucleic Acid Materials for Inducing Non-canonical Structures 230

13.5 Conclusion 231

References 232

14 Materials Science and Nanotechnology of Nucleic Acids 235

14.1 Introduction 235

14.2 Non-canonical Structure-Based Nanomaterials Resembling Protein Functions 235

14.2.1 Aptamer 235

14.2.2 DNAzyme 238

14.2.3 Ion Channel 240

14.3 Protein Engineering Using G4-Binding Protein 240

14.4 Regulation of Gene Expression by G4-Inducing Materials 242

14.5 Environmental Sensing 246

14.5.1 Sensing Temperature in Cells 246

14.5.2 Sensing pH in Cells 248

14.5.3 Sensing K+ Ion in Cells 248

14.5.4 Sensing Crowding Condition in Cells 249

14.6 Conclusion 250

References 250

15 Future Outlook for Chemistry and Biology of Non-canonical Nucleic Acids 253

15.1 Introduction 253

15.2 Exploring Potential: Properties of Non-canonical Structures in Unusual Media 253

15.3 Systemizing Properties: Prediction of the Formation of Non-canonical Nucleic Acids Structures 259

15.4 Advancing Technology: Applications of Non-canonical Structures Taking Concurrent Reactions into Account 262

15.4.1 Co-transcriptional Dynamics of G-Quadruplex 263

15.4.2 Co-transcriptional Functionalization of Riboswitch-Like Sensor 263

15.4.3 Co-transcriptional RNA Capturing for Selection of Functional RNAs 266

15.5 Conclusion 267

References 268

Index 271

Authors

Naoki Sugimoto