Note: Sequence-Specific DNA Binding Agents -- Contents -- Chapter 1 DNA Recognition by Triple Helix Formation -- 1.1 Introduction -- 1.1.1 Triplets and Triplex Motifs -- 1.2 Strategies to Increase Triplex Stability -- 1.2.1 Sugar Modifications -- 1.2.2 Addition of Positive Charges -- 1.2.3 Backbone Modifications -- 1.2.4 Base Stacking -- 1.2.5 Triplex-Binding Ligands -- 1.3 Overcoming the pH Dependency -- 1.3.1 Pyrimidine Base Analogues -- 1.3.2 Purine Base Analogues -- 1.4 Recognition of Pyrimidine Interruptions -- 1.4.1 Null Bases and Abasic Linkers -- 1.4.2 Natural Bases -- 1.4.3 Nucleotide Analogues for Recognizing Pyrimidine Interruptions -- 1.4.4 Nucleotide Analogues for Recognizing both Partners of the Base Pair -- 1.5 Mixed Sequence Recognition -- Acknowledgements -- References -- Chapter 2 Interfacial Inhibitors of Human Topoisomerase I -- 2.1 Introduction -- 2.2 Molecular Mechanism of Action of Drugs that Trap Top1 Cleavage Complexes -- 2.2.1 Intercalation between the Base Pairs Flanking the Top1-Mediated DNA Break -- 2.2.2 DNA Untwisting by Drugs at the Top1-Mediated DNA Cleavage Site -- 2.2.3 Common Hydrogen-Bond Network for Top1 Inhibitors Bound in the Ternary Complex -- 2.3 Generalization of the Interfacial Inhibitor Concept -- Acknowledgments -- References -- Chapter 3 Diversity of Topoisomerase I Inhibitors for Cancer Chemotherapy -- 3.1 Introduction -- 3.2 Camptothecins -- 3.3 Indenoisoquinolines -- 3.4 Benzimidazoles -- 3.5 Indolocarbazoles -- 3.6 Phenanthridines and Related Compounds -- 3.7 Marine Alkaloids -- 3.8 Plant Natural Products -- 3.9 Conclusion -- References -- Chapter 4 Slow DNA Binding -- 4.1 Introduction - Kinetics vs. Thermodynamics of DNA Binding -- 4.2 Different DNA-Binding Modes - Different DNA-Binding Kinetics -- 4.2.1 External Electrostatic Binding -- 4.2.2 Groove Binding -- 4.2.3 Intercalation. , 4.2.4 Threading Intercalation -- 4.3 Common Slow DNA Binders -- 4.3.1 Actinomycin D -- 4.3.2 Nogalamycin -- 4.4 Ruthenium Complexes Exhibiting Slow DNA Binding Kinetics -- 4.4.1 Bis-intercalating Ru-dimer [μ-c4(cpdppz)2(phen)4Ru2]4+ -- 4.4.2 Semirigid Ru-dimer [μ-(11,110-bidppz)(x)4Ru2]4+ (x=phen or bipy) -- References -- Chapter 5 DNA Gene Targeting using Peptide Nucleic Acid (PNA) -- 5.1 Introduction -- 5.2 Duplex DNA Recognition in vitro -- 5.3 PNA Conjugates -- 5.4 Effect of PNA Binding on DNA Structure -- 5.5 Cellular Gene Targeting -- 5.6 Activation of Gene Transcription -- 5.7 Gene-Targeted Repair -- 5.8 Cellular Delivery and Bioavailability in vivo -- 5.9 Prospects -- References -- Chapter 6 Actinomycin D: Sixty Years of Progress in Characterizing a Sequence-Selective DNA-Binding Agent -- 6.1 Summary -- 6.2 Introduction -- 6.2.1 Historical Perspectives -- 6.3 DNA-Binding Studies: The Early Years -- 6.3.1 The Intercalation Model -- 6.3.2 Sequence-Selectivity of Actinomycin D -- 6.4 Characterization of the Actinomycin D-DNA Complex -- 6.4.1 Role of Bases Flanking the Actinomycin D-Binding Site -- 6.4.2 Promiscuity in the Sequence Selectivity of Actinomycin D -- 6.5 Global vs. Microscopic Sequence-Recognition -- 6.5.1 The Shuffling Hypothesis Revisited -- 6.6 Structural Motifs as Actinomycin D Targets -- 6.6.1 The Era of Single-Strand DNA Binding -- 6.7 Conclusions -- Acknowledgments -- References -- Chapter 7 Thermal Denaturation of Drug-DNA Complexes: Tools and Tricks -- 7.1 Introduction -- 7.2 Thermal Denaturation Tools -- 7.2.1 Analysis of Tm Shifts in the Presence of Drug -- 7.2.2 Obtaining Binding Enthalpy Values by DSC -- 7.2.3 Modeling Melting Curves by McGhee's Algorithm -- 7.2.4 Case Studies: Bisintercalating Anthracyclines and Echinomycin -- 7.2.5 Summary: Advantages and Pitfalls -- 7.3 Thermal Denaturation: New Tricks. , 7.3.1 Melting Mixtures to Assess Sequence- and Structural-Selectivity -- 7.3.2 Advantages and Prospects -- 7.4 Summary -- Acknowledgments -- References -- Chapter 8 Computer Simulations of Drug-DNA interactions: A Personal Journey -- 8.1 Introduction -- 8.2 Minor Groove DNA Binders -- 8.3 Natural Bifunctional Intercalators and Hoogsteen Base Pairing -- 8.4 Bis-Intercalation of Echinomycin and Related Bifunctional Agents in Relation to Binding Sequence Preferences -- 8.5 Binding Preferences of Synthetic Pyridocarbazole Bis-Intercalators -- 8.6 Sequence Selectivity of Actinomycin D -- 8.7 Binding of the Potent Antitumour Agent Trabectedin to DNA -- 8.8 Lamellarins as Topoisomerase I Poisons -- 8.9 Concluding Remarks -- Acknowledgements -- References -- Chapter 9 The Discovery of G-Quadruplex Telomere Targeting Drugs -- 9.1 Introduction -- 9.2 Anthraquinones and Intercalation into Duplex DNA -- 9.3 Interactions with Higher-Order DNA -- 9.4 Telomerase and Cancer -- 9.5 First-Generation G-Quadruplex Ligands -- 9.6 Molecular Models for Quadruplex-Trisubstituted Acridine Complexes -- 9.7 Cellular and Pharmacological Properties of Trisubstituted Acridines -- 9.8 Conclusions -- Acknowledgements -- References -- Chapter 10 The Mechanism of Action of Telomestatin, a G-Quadruplex-Interactive Compound -- 10.1 Introduction -- 10.1.1 Telomere Structure in Mammals and Telomerase -- 10.1.2 Mechanism of Inhibition of Telomerase by Telomestatin -- 10.1.3 The Stoichiometry of Binding of Telomestatin to the Human Telomeric G-Quadruplex -- 10.1.4 Identity of the Telomeric G-Quadruplex Formed in the Presence of Telomestatin -- 10.1.5 Proposed Models for Telomestatin Binding to the Human Telomeric G-Quadruplex Structure -- 10.1.6 Potential Effect of Telomestatin on the Assembly of Telomeres into Higher-Order Structures. , 10.1.7 Genomic Instability Caused by Telomestatin Treatment and Activation of DNA Damage Response -- 10.1.8 Other Mechanisms of Telomestatin in Mediating its Biological Activity -- 10.2 Concluding Remarks -- Acknowledgments -- References -- Chapter 11 Structural Features of the Specific Interactions between Nucleic Acids and Small Organic Molecules -- 11.1 Introduction -- 11.2 Diels-Alder Ribozymes -- 11.3 Theophylline and Flavin Mononucleotide Binding -- 11.4 Purine Riboswitches -- 11.5 Adenosine Monophosphate Binding -- 11.6 Conclusions -- 11.7 Perspectives -- References -- Subject Index.