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
