Enzymatic and chemical synthesis of nucleic acid derivatives /
edited by Jesús Fernández-Lucas, María-José Camarasa Rius.
- xiii, 334 pages : illustrations (some color) ; 26 cm
ABOUT THE AUTHOR Jesús Fernández-Lucas, PhD, is a tenured professor at the European University of Madrid, where he leads the Applied Biotechnology research group. His research is focused on the design and application of novel biocatalysts for the enzymatic synthesis of nucleosides.
María José Camarasa Rius, PhD, is Full Professor at the Medicinal Chemistry Institute of the Spanish National Research Council (IQM-CSIC) in Madrid, working on the design of novel enzymatic inhibitors with potential anticancer, antifungal and antiviral activity.
Includes bibliographical references and index.
TABLE OF CONTENTS 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
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
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 2′F-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
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.