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Enzymatic and Chemical Synthesis of Nucleic Acid Derivatives

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Enzymatic and Chemical Synthesis of Nucleic Acid Derivatives

Jesús Fernández Lucas (Editor), María-José Camarasa Rius (Editor)

ISBN: 978-3-527-34376-8 April 2019 352 Pages

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Description

A review of innovative tools for creative nucleic acid chemists that open the door to novel probes and therapeutic agents

Nucleic acids continue to gain importance as novel diagnostic and therapeutic agents. With contributions from noted scientists and scholars, Enzymatic and Chemical Synthesis of Nucleic Acid Derivatives is a practical reference that includes a wide range of approaches for the synthesis of designer nucleic acids and their derivatives.

The book covers enzymatic (including chemo-enzymatic) methods, with a focus on the synthesis and incorporation of modified nucleosides. The authors also offer a review of innovative approaches for the non-enzymatic chemical synthesis of nucleic acids and their analogs and derivatives, highlighting especially challenging species. The book offers a concise review of the methods that prepare novel and heavily modified polynucleotides in sufficient amount and purity for most clinical and research applications. This important book:

-Presents a timely and topical guide to the synthesis of designer nucleic acids and their derivatives
-Addresses the growing market for nucleotide-derived pharmaceuticals used as anti-infectives and chemotherapeutic agents, as well as fungicides and other agrochemicals.
-Covers novel methods and the most recent trends in the field
-Contains contributions from an international panel of noted scientistics

Written for biochemists, medicinal chemists, natural products chemists, organic chemists, and biotechnologists, Enzymatic and Chemical Synthesis of Nucleic Acid Derivatives is a practice-oriented guide that reviews innovative methods for the enzymatic as well as non-enzymatic synthesis of nucleic acid species.

Preface xi

1 Enzymatic Synthesis of Nucleoside Analogues by Nucleoside Phosphorylases 1
Sarah Kamel, Heba Yehia, Peter Neubauer, and AnkeWagner

1.1 Introduction 1

1.1.1 Nucleosides and Nucleoside Analogues 1

1.1.2 Enzymes Involved in the Enzymatic Synthesis of Nucleoside Analogues 3

1.2 Nucleoside Phosphorylases 3

1.2.1 Classification and Substrate Spectra of Nucleoside Phosphorylases 3

1.2.1.1 Nucleoside Phosphorylase-I Family 4

1.2.1.2 Nucleoside Phosphorylase-II Family 6

1.2.2 Limitations in the Current Classification 7

1.2.3 Reaction Mechanism 8

1.2.4 Domain Structure and Active Site Residues of Nucleoside Phosphorylases 9

1.2.4.1 NP-I Family Members 9

1.2.4.2 NP-II FamilyMembers 10

1.3 Enzymatic Approaches to Produce Nucleoside Analogues Using Nucleoside Phosphorylases 11

1.3.1 One-pot Two-Step Transglycosylation Reaction 11

1.3.2 Pentofuranose-1-phosphate as Universal Glycosylating Substrate for Nucleoside Phosphorylase (NP) 12

1.3.2.1 Nucleoside Synthesis from Chemically Synthesized Pentose-1P 12

1.3.2.2 Nucleosides Synthesis from d-Glyceraldehyde-3-phosphate 13

1.3.2.3 Nucleoside Synthesis from d-Pentose 13

1.3.2.4 Nucleoside Synthesis from Enzymatically Produced Pentose-1P 13

1.4 Approaches to Produce Nucleoside Analogues 14

1.4.1 Whole Cell Catalysis 14

1.4.2 Crude Enzyme Extract 15

1.4.3 Application of Purified Enzymes 15

1.4.3.1 Immobilized Enzymes 16

1.4.3.2 Enzyme Reactors 17

1.5 Upscaling Approaches for the Production of Nucleoside Analogues 18

1.6 Production of Pharmaceutically Active Compounds by Nucleoside Phosphorylases 18

1.7 Outlook for the Application of Nucleoside Phosphorylase in the Production of Nucleoside Analogues 19

References 20

2 Enzymatic Phosphorylation of Nucleosides 29
Daniela Ubiali and Giovanna Speranza

2.1 Introduction 29

2.2 Nonspecific Acid Phosphatases (NSAPs) 30

2.3 Deoxyribonucleoside Kinases (dNKs) 33

2.4 Conclusion 37

References 37

3 Enzymatic Synthesis of Nucleic Acid Derivatives UsingWhole Cells 43
Elizabeth S. Lewkowicz and AdolfoM. Iribarren

3.1 Introduction 43

3.2 Nucleoside Synthesis Mediated by Microbial Nucleoside Phosphorylases 45

3.3 Nucleoside Analogues Synthesis by the Combined Action of Microbial Nucleoside Phosphorylases and Other Enzymes 48

3.3.1 Nucleoside Phosphorylases Coupled to Deaminases 48

3.3.2 Nucleoside Phosphorylases Coupled to Phosphopentomutase 48

3.3.3 Nucleoside Phosphorylases Coupled to Phosphopentomutase and Other Enzymes 49

3.3.4 Nucleoside Phosphorylases Coupled to Other Enzymes 51

3.4 Chemoenzymatic Preparation of Nonconventional Nucleoside Analogues Involving Whole Cell Biocatalyzed Key Steps 51

3.4.1 l-Nucleosides 52

3.4.2 Carbocyclic Nucleosides 55

3.4.3 C-Nucleosides 56

3.5 Nucleoside Prodrugs Preparation by Whole Cell Systems 57

3.5.1 Acylnucleosides 57

3.5.2 Nucleoside Phosphates 59

3.6 Other Nucleoside Derivatives 61

3.6.1 NDP 61

3.6.2 NDP-sugar 61

3.7 Perspectives 65

References 65

4 Enzymatic Synthesis of Nucleic Acid Derivatives by Immobilized Cells 79
Jorge A. Trelles, CintiaW. Rivero, Claudia N. Britos, and María J. Lapponi

4.1 Introduction 79

4.2 Nucleic Acid Derivatives 81

4.3 Whole Cell Immobilization: Generalities 85

4.4 Synthesis of Nucleosides by Immobilized Cells 86

4.4.1 Natural Nucleoside Synthesis 87

4.4.2 Nucleoside Analogues Synthesis 88

4.4.3 Nucleoside Analogues Derivatives Synthesis 92

4.5 Conclusion 98

References 98

5 Enzymatic Synthesis of Nucleic Acid Derivatives by Immobilized Enzymes 107
Jesús Fernández-Lucas andMiguel Arroyo

5.1 Introduction 107

5.2 Immobilized Glycosyltransferases 108

5.2.1 Immobilized Nucleoside Phosphorylases 108

5.2.1.1 Stabilization of Nucleoside Phosphorylases by Immobilization 108

5.2.1.2 Synthesis of Nucleosides Catalyzed by Immobilized Nucleoside Phosphorylases 109

5.2.2 Immobilized Nucleoside 2′-Deoxyribosyltransferases 111

5.2.2.1 Stabilization of Nucleoside 2′-Deoxyribosyltransferases by Immobilization 113

5.2.2.2 Synthesis of Nucleosides Catalyzed by Immobilized

2′-Deoxyribosyltransferases 114

5.2.3 Immobilized Nucleobase Phosphoribosyltransferases 116

5.3 Immobilized Nucleoside Oxidase 117

5.4 Immobilized Hydrolases 118

5.4.1 Immobilized Lipases 118

5.4.2 Immobilized Proteases 120

5.4.3 Immobilized Esterases 121

5.4.4 Immobilized Deaminases 121

5.4.5 Immobilized S-Adenosylhomocysteine Hydrolases 122

5.5 Immobilized Phosphopentomutases 122

5.6 Immobilized Deoxyribonucleoside Kinases 123

References 124

6 Synthesis of Nucleic Acid Derivatives by Multi-Enzymatic Systems 129
Qingbao Ding

6.1 Multi-Enzymatic Systems in Biosynthesis 129

6.2 General Overview of Multi-Enzymatic Synthesis of Nucleic Acid

Derivatives 131

6.3 Multi-Enzymatic Synthesis of Nucleosides and Their Derivatives 132

6.3.1 Multi-Enzymatic Synthesis of Nucleosides and Their Analogues by

Nucleoside Phosphorylase 132

6.3.2 Transglycosylation Coupled with Xanthine Oxidase 134

6.3.3 Transglycosylation Reactions Coupled with Deamination 135

6.3.4 ADase in Combination with Lipase 136

6.3.5 Esterification of Nucleosides 138

6.3.6 Multi-Enzymatic Synthesis of Fluorine Nucleosides 140

6.3.7 Multi-Enzymatic Synthesis of Nucleosides via R5P 142

6.3.8 Other Reactions 144

6.4 Multi-Enzymatic Synthesis of Nucleotides and Their Derivatives 145

6.4.1 Multi-Enzymatic Synthesis of NMPs and dNMPs 146

6.4.2 Multi-Enzymatic Synthesis of NTPs and dNTPs 147

6.4.3 Multi-Enzymatic Synthesis of NDP-Sugars and Other NDP

Derivatives 148

6.5 Conclusion 150

References 151

7 Enzymatic Synthesis Using Polymerases of Modified Nucleic Acids and Genes 159
Elena Eremeeva and Piet Herdewijn

7.1 Introduction 159

7.2 Types of XNA Biomolecules 161

7.3 Enzymatic Synthesis of XNA and DNA Polymerases 161

7.4 Base-Modified XNAs (Base-XNAs) 167

7.4.1 Nucleobase Analogues 167

7.4.1.1 Non-Canonical Nucleotides 167

7.4.1.2 Amino-acid-Like Groups 174

7.4.1.3 Functional Tags 176

7.4.2 Unnatural Base Pairs 177

7.4.2.1 Hydrogen-Bonding Base Pairs 177

7.4.2.2 Hydrophobic Base Pairs 179

7.5 Sugar-Modified XNAs (Sugar-XNAs) 180

7.5.1 Pentose-XNA 180

7.5.2 2′-Ribose-XNA 182

7.6 Phosphodiester Backbone-XNA 183

7.7 A Mirror-Image l-DNA 184

7.8 Conclusions 184

References 185

8 Synthetic Approaches to the Fleximer Class of Nucleosides – A Historic Perspective 195
Therese C. Ku and Katherine Seley-Radtke

8.1 Distal Fleximers 198

8.1.1 Ribose Distal Fleximers 198

8.1.2 2′-Deoxyribose Distal Fleximers 201

8.1.3 2′-Modified Distal Fleximers 209

8.2 Proximal Fleximers 209

8.2.1 Ribose Proximal Fleximers 209

8.2.2 2′-Deoxyribose Proximal Fleximers 215

8.2.3 Carbocyclic Proximal Fleximers 216

8.2.4 Proximal Fleximers from Other Groups 218

8.3 “Reverse” Fleximers 222

8.4 Acyclic Fleximers 226

8.5 Conclusion 228

References 229

9 Synthesis of Oligonucleotides Carrying Nucleic Acid Derivatives of Biomedical and Structural Interest 237
Ramon Eritja, Anna Aviñó, Carme Fàbrega, Adele Alagia, Andreia F. Jorge, and

Santiago Grijalvo

9.1 Introduction 237

9.2 Oligonucleotides Carrying the DNA Lesion O6-Alkylguanine 238

9.3 The Effect of Chemical Modifications in Non-Canonical DNA

Structures 240

9.3.1 Triplex-Forming Oligonucleotides 241

9.3.2 G-quadruplex-Forming Oligonucleotides 243

9.3.3 Oligonucleotides Forming i-Motif Structures 245

9.4 Modified siRNAs for Gene Silencing 246

9.4.1 Modifications of the 3′-Overhangs 246

9.4.2 Modifications of the 5′-End 249

References 251

10 Synthesis of Carbohydrate–Oligonucleotide Conjugates and Their Applications 259
Juan C. Morales

10.1 Introduction 259

10.2 Synthesis of COCs 260

10.2.1 On-Support Synthesis 260

10.2.1.1 Phosphoramidite Chemistry 261

10.2.1.2 Derivatization of Nucleoside Base Residues 261

10.2.1.3 Oximation Chemistry 263

10.2.1.4 Amide Chemistry 263

10.2.1.5 Urea Chemistry 264

10.2.1.6 CuAAC Chemistry 264

10.2.2 Solution-Phase Conjugation 265

10.2.2.1 Disulfide Formation 265

10.2.2.2 Nucleophilic Addition on Unsaturated Carbon 265

10.2.2.3 Carbonyl Addition–Elimination Reaction 267

10.2.2.4 CuAAC Chemistry 267

10.2.2.5 Diazocoupling Reaction 267

10.2.2.6 Amide Bond Formation 267

10.2.2.7 Enzymatic Incorporation of Saccharides or Nucleotides 268

10.3 Synthesis of Glycocluster Oligonucleotides 268

10.3.1 dsDNA Scaffolds 269

10.3.2 Non-Canonical DNA Scaffolds (G4 and three-Way Junction) 269

10.3.3 Organic Spacer Scaffolds 270

10.3.4 Biomolecules as Scaffolds 271

10.4 Applications of COCs 273

10.4.1 Improving Cellular Uptake 273

10.4.2 Molecular Interactions Probes 279

10.4.3 Lectin Binding and Glycoarrays 280

10.5 Outlook 281

References 281

11 Advances in Light-Directed Synthesis of High-Density Microarrays and Extension to RNA and 2F-ANA Chemistries 291
Jory Lietard,Masad J. Damha, andMarkM. Somoza

11.1 Introduction 291

11.2 Phosphoramidite Chemistry Applied to the Photolithographic

Synthesis of Microarrays 293

11.3 Recent Improvements in the Synthesis of DNA Microarrays 295

11.4 Synthesis of RNA Microarrays 300

11.5 Enzymatic Approaches to RNA Array Synthesis 305

11.6 Synthesis of 2′F-ANA Microarrays 306

11.7 Conclusion and Outlook 309

References 310

12 SAMHD1-Mediated Negative Regulation of Cellular dNTP Levels: HIV-1, Innate Immunity, and Cancers 313
TatsuyaMaehigashi, Dong-Hyun Kim, Raymond F. Schinazi, and Baek Kim

12.1 Cellular dNTP Concentrations 313

12.2 SAMHD1 and Negative Regulation of Cellular dNTPs 314

12.3 SAMHD1 Substrates, Activators, and Inhibitors 316

12.4 SAMHD1 and HIV-1 Reverse Transcription 318

12.5 SAMHD1 Mutations and Innate Immunity 318

12.6 SAMHD1 and Cancers 321

12.7 Summary 321

Acknowledgment 322

References 322

Index 327