With extensive coverage of synthesis techniques and applications, this text describes chemical biology techniques which have gained significant impetus during the last five years. It focuses on the methods for obtaining modified and native nucleic acids, and their biological applications. Topics covered include:chemical synthesis of modified RNAexpansion of the genetic alphabet in nucleic acids by creating new base pairschemical biology of DNA replication: probing DNA polymerase selectivity mechanisms with modified nucleotidesnucleic-acid-templated chemistrychemical biology of peptide nucleic acids (PNA)the interactions of small molecules with DNA and RNAthe architectural modules of folded RNAsgenesis and biological applications of locked nucleic acid (LNA)small non-coding RNA in bacteriamicroRNA-guided gene silencingnucleic acids based therapiesinnate immune recognition of nucleic acidlight-responsive nucleic acids for the spatiotemporal control of biological processesDNA methylationframeworks for programming RNA devicesRNA as a catalyst: The Diels-Alderase-Ribozymeevolving an understanding of RNA function byin vitro approachesthe chemical biology of aptamers: synthesis and applicationsnucleic acids as detection toolsbacterial riboswitch discovery and analysis

The Chemical Biology of Nucleic Acids is an essential compendium of the synthesis of nucleic acids and their biological applications for bioorganic chemists, chemical biologists, medicinal chemists, cell biologists, and molecular biologists.

Günter Mayer, Assistant Professor, LIMES Prog. Unit Chemical Biology and Medicinal Chemistry, Kekulé-Institute for Organic Chemistry and Biochemistry, University of Bonn, GermanyProfessor Mayer's research involves molecular diversity applied to elucidate the conformation, function and identity of biomolecules. He is a co-founder of NascaCell Technologies AG, a leading service provider of innovative biomolecules, where he headed the combinatorial biotechnology department. He has published papers in leading journals such asNature, Angewandte Chemie andJournal of the American Chemical Society.

Foreword vii

Preface ix

List of Contributors xi

1 Chemical Synthesis of Modified RNA 1Claudia Höbartner and Falk Wachowius

2 Expansion of the Genetic Alphabet in Nucleic Acids by Creating New Base Pairs 39Ichiro Hirao and Michiko Kimoto

3 Chemical Biology of DNA Replication: Probing DNA Polymerase Selectivity Mechanisms with Modified Nucleotides 63Andreas Marx

4 Nucleic Acid-templated Chemistry 73Michael Oberhuber

5 Chemical Biology of Peptide Nucleic Acids (PNAs) 103Peter E. Nielsen

6 The Interactions of Small Molecules with DNA and RNA 115Yun Xie, Victor K. Tam and Yitzhak Tor

7 The Architectural Motifs of Folded RNAs 141Valérie Fritsch and Eric Westhof

8 Genesis and Biological Applications of Locked Nucleic Acids (LNAs) 175Harleen Kaur and Souvik Maiti

9 Small Non-coding RNA in Bacteria 199Sabine Brantl

10 MicroRNA-guided Gene Silencing 223Gunter Meister

11 Nucleic Acid-based Therapies 233Britta Hoehn and John J. Rossi

12 Innate Immune Recognition of Nucleic Acids 261Stefan Bauer

13 Light-responsive Nucleic Acids for the Spatiotemporal Control of Biological Processes 279Alexander Heckel and Günter Mayer

14 DNA Methylation 307Albert Jeltsch and Renata Z. Jurkowska

15 Frameworks for Programming RNA Devices 323Maung Nyan Win, Joe C. Liang and Christina D. Smolke

16 RNA as a Catalyst: The DielsAlderase Ribozyme 339Andres Jäschke

17 Evolving an Understanding of RNA Function by In Vitro Approaches 355Qing Wang and Peter J. Unrau

18 The Chemical Biology of Aptamers: Synthesis and Applications 377Günter Mayer and Bernhard Wulffen

19 Nucleic Acids as Detection Tools 401Jeffrey C.F. Lam, Sergio Aguirre and Yingfu li

20 Bacterial Riboswitch Discovery and Analysis 433Tyler D. Ames and Ronald R. Breaker

Index 455