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• Title:DNA-targeting molecules as therapeutic agents / Edited by Michael J. Waring.
  
•    
• Other Contributors/Collections:Waring, Michael J., editor.
  Royal Society of Chemistry (Great Britain), issuing body.
  
• Published/Created:[Cambridge] : Royal Society of Chemistry, [2018]
  

• Holdings

  Holdings Record Display

  • Location:WOODWARD LIBRARY stacksWhere is this?
    
  • Call Number: QU560 .D629 2018
    
  • Number of Items:1
    
  • Status:Available
    

   
• Library of Congress Subjects:Gene therapy.
  DNA-drug interactions.
  
• Medical Subjects: Genetic Therapy.
  DNA--drug effects.
  
• Description:xvii, 414 pages ; 24 cm
  
• Series:Chemical biology series ; no. 7.
  
• Summary:This book explains key aspects of the progress that has been made towards understanding how drugs can bind specifically to nucleic acids, and thus underpin the endeavour to make gene targeting a reality. The binding of drugs to DNA is a fast developing area of research with important applications in medicine, particularly the treatment of cancer. Early chapters cover methodologies to evaluate DNA-interactive agents and then the book provides examples of DNA-interactive molecules and technologies in development as therapeutic agents and treats in depth topics such as DNA-binding metal complexes, peptide and polyamide-DNA interactions.
  
• Notes:Includes bibliographical references and index.
  
• ISBN:9781782629924 hardcover
  1782629920 hardcover
  
• Contents:Machine generated contents note: ch. 1 DNA Recognition by Parallel Triplex Formation / David A. Rusting
  1.1. Why Triplexes?
  1.1.1. Triplets and Triplex Motifs
  1.1.2. Base, Sugar and/or Phosphate Modifications
  1.2. Stabilising Triplexes
  1.2.1. Enhancing Stacking and Hydrophobic Interactions
  1.2.2. Locking the Sugar Pucker
  1.2.3. Adding Positive Charge(s)
  1.2.4. Removing Negative Charge(s)
  1.2.5. Triplex-binding and Cross-linking Agents
  1.3. Decreasing pH Dependence
  1.3.1. Pyrimidine Analogues
  1.3.2. Purine Analogues
  1.4. Recognising Pyrimidine-Purine Base Pairs
  1.4.1. Null Bases and Abasic Linkers
  1.4.2. Natural Bases
  1.4.3. Analogues for CG Recognition
  1.4.4. Analogues for TA Recognition
  1.4.5. Other Approaches
  1.5. Towards Mixed Sequence Recognition at Neutral pH
  1.6. Outlook
  Acknowledgements
  References
  ch. 2 Interfacial Inhibitors / Yves Pommier
  2.1. Introduction
  2.2. Case Studies
  2.2.1. Topoisomerase Inhibitors
  2.2.2. HIV Integrase Strand Transfer Inhibitors
  2.2.3. STING Inhibitors
  2.2.4. Arp2-3 Inhibitors
  2.3. Prospects
  Acknowledgements
  References
  ch. 3 Slow DNA Binding / Bengt Norden
  3.1. Introduction
  -Kinetics vs. Thermodynamics of DNA Binding
  3.2. Different DNA Binding Modes
  -Different DNA Binding Kinetics
  3.2.1. External Electrostatic Binding
  3.2.2. Groove Binding
  3.2.3. Intercalation
  3.2.4. Threading Intercalation
  3.3. Common Slow DNA Binders
  3.3.1. Actinomycin D
  3.3.2. Nogalamycin
  3.4. Ruthenium Complexes Exhibiting Slow DNA-binding Kinetics
  3.4.1. Bis-intercalating Ru-dimer [μ-c4(cpdppz)2(phen)4Ru2]4+
  3.4.2. Semirigid Ru-dimer [μ.-(11,11'-bidppz)(x)4Ru2]4+ (x=phen or bipy)
  3.5. Addendum to Second Edition
  References
  ch. 4 Thermal Denaturation of Drug-DNA Complexes / Jonathan B. Chaires
  4.1. Introduction
  4.2. Thermal Denaturation Tools
  4.2.1. Analysis of Tm shifts in the Presence of Drug
  4.2.2. Obtaining Binding Enthalpy Values by DSC
  4.2.3. Modeling Melting Curves by McGhee's Algorithm
  4.2.4. Case Studies: Bisintercalating Anthracyclines and Echinomycin
  4.2.5. Summary: Advantages and Pitfalls
  4.3. High-throughput Thermal Denaturation Approaches
  4.3.1. Differential Scanning Fluorimetry
  4.3.2. DSC Compared with DSF: Slow and Expensive but Definitive
  4.3.3. Illustrations of Differential Scanning Fluorimetry Data and Utility
  4.3.4. Advantages and Prospects
  4.4. Summary
  Acknowledgements
  References
  ch. 5 Computer Simulations of Drug-DNA Interactions: A Personal Journey / Federico Gago
  5.1. Introduction
  5.2. Minor Groove DNA Binders
  5.3. Natural Bifunctional Intercalators and Hoogsteen Base Pairing
  5.4. Bis-intercalation of Echinomycin and Related Bifunctional Agents in Relation to Binding Sequence Preferences
  5.5. Binding Preferences of Synthetic Pyridocarbazole Bis-intercalators
  5.6. Sequence Selectivity of Actinomycin D
  5.7. Binding of the Potent Antitumor Agent Trabectedin to DNA
  5.8. Other Examples of DNA Minor-groove-bonding Tetrahydroisoquinoline Antibiotics
  5.9. Melting DNA on the Computer
  5.10. Mitomycin Bis-adduct Formation as a Test Case for QM/MM Methods
  5.11. Lamellarins as Topoisomerase I Poisons
  5.12. Concluding Remarks
  Acknowledgements
  References
  ch. 6 Binding of Small Molecules to Trinucleotide DNA Repeats Associated with Neurodegenerative Diseases / Chung-ke Chang
  6.1. Introduction
  6.1.1. Trinucleotide Repeat DNA
  6.1.2. Diseases Associated with Expansion of Repetitive DNA
  6.1.3. Molecular Mechanism of TNR Expansion
  6.2. Interaction of DNA-binding Drugs with Triplet Repeats Connected with Neurological Diseases
  6.2.1. Actinomycin D
  6.2.2. Aureolic Acid-type Metallo-ligands
  6.2.3. Pyrene-functionalized Pyrrole-Imidazole Polyamides
  6.2.4. Naphthyridine and Its Analogues
  6.2.5. Bulge-binding Agents
  6.2.6. Triptycene- and Acridine-based Ligands
  6.3. Conclusion
  References
  ch. 7 Parsing the Enthalpy-Entropy Compensation Phenomenon of General DNA-Ligand Interactions by a `Gradient Determinant' Approach / Leung Sheh
  7.1. Introduction
  7.1.1. Footprinting Analysis of DNA-Peptide Sequence-selective Interactions
  7.1.2. Circular Dichroism Analysis of DNA-Peptide Interactions
  7.1.3. Investigations of Enthalpy-Entropy Compensation Phenomena in General DNA-Ligand Interactions
  7.2. Conclusions Regarding the EEC Phenomenon of General DNA-Ligand Interactions
  Acknowledgements
  References
  ch. 8 Structural Studies of DNA-binding Metal Complexes of Therapeutic Importance / James P. Hall
  8.1. Introduction-Ruthenium Complexes as DNA Probes and DNA Damage Agents
  8.2. Versatility of Ruthenium Polypyridyl Complexes
  8.2.1. Early Spectroscopic Studies
  8.3. PACT and PDT
  8.3.1. Therapeutic Relevance
  8.4. Intercalation by Ruthenium
  dppz Complexes
  8.4.1. B-DNA Duplexes
  -Intercalation Geometries and Sequence Specificities
  8.4.2. Lambda Enantiomer
  8.4.3. Semi-intercalation
  8.4.4. Symmetrical Intercalation
  8.4.5. Delta Enantiomer
  8.4.6. Racemic Binding
  8.5. Binding of Ru-polypyridyl Complexes to DNA G-quadruplexes
  8.5.1. Quadruplex Binding
  -Mononuclear Complexes
  8.5.2. Quadruplex Binding-Binuclear Complexes
  8.6. Summary and Future Outlook
  Acknowledgements
  References
  ch. 9 Therapeutic Potential of DNA Gene Targeting using Peptide Nucleic Acid (PNA) / Peter E. Nielsen
  9.1. Introduction
  9.2. Duplex DNA Recognition In Vitro
  9.3. PNA Conjugates
  9.4. Effect of PNA Binding on DNA Structure
  9.5. Cellular Delivery and Tissue Bioavailability In Vivo
  9.6. Cellular Gene Targeting
  9.7. Activation of Gene Transcription
  9.8. Gene-targeted Repair
  9.9. In Vivo Gene Targeting and Repair by PNA Oligomers
  9.10. Therapeutic Prospects
  References
  ch. 10 Sequence-selective Interactions of Actinomycin D with DNA: Discovery of a Thermodynamic Switch / David E. Graves
  10.1. Summary
  10.2. Introduction
  10.3. DNA Sequence Dictates Binding Energetics
  10.3.1. Energetic Mechanism Is Sequence-dependent
  10.3.2. Mode of Binding is Intercalation
  10.4. DNA Sequence Effects on Kinetics
  10.4.1. Dissociation Kinetics Properties
  10.4.2. Association Kinetics Controlled by DNA Sequence
  10.4.3. Linkage of Energetics and Kinetics to the Shuffling Model
  10.5. Discussion
  10.6. Summary
  References
  ch. 11 Molecular Modelling Approaches for Assessing Quadruplex-Small Molecule Interactions / Stephen Neidle
  11.1. Introduction
  11.1.1. Brief Overview of Quadruplexes
  11.2. G-quadruplex Stabilising Ligands
  11.3. Some Basic Molecular Modelling Approaches
  11.3.1. Molecular Docking Procedures
  11.3.2. Classical Molecular Dynamics Simulations
  11.4. Force Fields for Quadruplexes
  11.4.1. Long-range Electrostatic Interactions
  11.4.2. Base Stacking and Backbone Descriptions
  11.4.3. Molecular Docking and Dynamic Simulations of DNA and RNA Quadruplex-Ligand Complexes
  -Some Examples
  11.5. Enhanced Sampling Methods
  11.5.1. Simulated Annealing Algorithms
  11.5.2. Principal Component Analysis
  11.5.3. Free-energy Calculations
  11.5.4. Umbrella Sampling
  11.5.5. Markov State Models
  11.6. Conclusions
  Acknowledgements
  References
  ch. 12 Molecular Recognition of DNA by Py-Im Polyamides: From Discovery to Oncology / Paul B. Finn
  12.1. Introduction
  -DNA-targeted Therapeutics
  12.2. Pairing Rules in the Minor Groove
  12.3. Hairpin Structure
  12.4. Binding Site Size: β- β, Im-β and Py-β Pairs
  12.5. γ-Hairpin Turn and Orientation Preference
  12.6. C-terminus of the Hairpin
  12.7. Second Generation Heterocycles for DNA Recognition
  12.8. Synthetic Methods
  12.9. Disruption of Transcription Factor-DNA Interface
  12.10. Inhibition of RNA Polymerase II Elongation
  12.11. Cell Permeation and Nuclear Localisation
  12.12. Gene Regulation in Cell Culture
  12.13. Global Sequence Analysis of Sequence Specificity
  12.14. Animal Studies: Pharmacokinetics and Toxicity
  12.15. Xenograft Cancer Models
  12.16. Formulation
  Acknowledgements
  References
  ch. 13 Synthetic Peptides for DNA Recognition Inspired by Transcription Factors / Annemieke Madder
  13.1. Transcription Factors as Source of Inspiration for the Design of DNA-binding Peptides
  13.1.1. Interaction Between dsDNA and Proteins: A Key Factor Regulating Transcription
  13.1.2. Families of Transcription Factors
  13.1.3. Detailed Analysis of the Primary and Secondary Structures of the GCN4 TF Bound to Its Target DNA as a Basis for the Design of Synthetic DNA-binding Mimics
  13.2. Design and Synthesis of TF Mimics as DNA Binding Peptides
  13.2.1. Design of TF Mimics: Replacement of the Dimerization Domain by Non-peptide Scaffolds
  13.2.2. Moving Away From Dimer-based Major Groove Binding: Miscellaneous Peptide Conjugates for Combined Major and Minor Groove Recognition
  13.2.3. Further Structure Minimisation: Monomeric Stapled Peptides as GCN4 TF Mimics
  13.2.4. Increasing the Therapeutic Potential: Cell-uptake Studies and Enhanced Proteolytic Stability
  13.3. Conclusions and Considerations for Future Design
  Acknowledgements
  References
  Contents note continued: ch. 14 Targeting DNA Mismatches with Coordination Complexes / Kelsey M. Boyle
  14.1. Introduction
  -Transition Metal Complexes as Non-covalent Probes for Nucleic Acids
  14.2. Rhodium Metalloinsertors: Probes for DNA Mismatches
  14.3. Rhodium Metalloinsertors in the Cell
  14.4. Luminescent Ruthenium Complexes as Probes for DNA Mismatches
  14.5. Conclusions and Future Directions
  Acknowledgements
  References
  ch. 15 CRISPR Highlights and Transition of Cas9 into a Genome Editing Tool / Thomas Bentin
  15.1. Introduction
  15.2. Discovery of CRISPR
  15.3. CRISPRs Contain Foreign DNA Elements, Suggesting a Role in Immunity
  15.4. Functional Demonstration of CRISPR-dependent Acquired Immunity
  15.5. Target for CRISPR Interference
  15.6. Cas9, crRJNA and tracrRNA: Discovery and Significance
  15.7. Biochemistry of type II CRISPR-Cas-mediated DNA Cleavage
  15.8. First Human Cell Genome Editing Using CRISPR-Cas9
  15.9. DNA Target Specificity of Cas9
  15.10. High-fidelity CRISPRs
  15.11. DSB Repair Pathway Recruitment
  15.12. Therapeutics
  References.