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DNA has been known to be the cellular target for many cytotoxic anticancer agents for several decades. The knowledge of its structure in atomic detail and the ease with which DNA fragments (both synthetic oligonucleotides and natural sequences) can be prepared and manipulated has aided the design of compounds that bind to it with improved sel- tivity. On the basis of this information, new generations of sequence reading compounds (including triplex forming oligonucleotides and minor groove binding ligands) have been prepared, which have the potential for targeting specifc DNA sequences as anti-gene agents. Within the last 10 years, it has also become apparent that the familiar DNA duplex is not the only structure that can be targeted by DNA-binding ligands and there has been increased interest in triplex and quadruplex structures as drug targets, as well as protein- DNA complexes, such as those with nucleosomes or topoisomerases. Each of these advances has required the availability and development of an arsenal of techniques for probing the interactions in both qualitative and quantitative terms. This v- ume of Methods in Molecular Biology brings together several techniques that are currently useful for examining these interactions. Some of these are updates on ones that were included in the earlier volume (Methods in Molecular Biology 90), published 12 years ago, while others are new.

Drug-DNA Interaction Protocols

Drug-DNA Interaction Protocols, Second Edition
Editor: Keith R. Fox, PhD


Contents
Preface
Contributors
1. Quantitative Analysis of Small Molecule- Nucleic Acid Interactions with a Biosensor Surface and Surface Plasmon Resonance Detection
Yang Liu and W. David Wilson
2. Thermal Melting Studies of Ligand DNA Interactions
Aurore Guédin, Laurent Lacroix, and Jean-Louis Mergny
3. Circular and Linear Dichroism of Drug-DNA Systems
Alison Rodger
4. Drug Binding to DNA-RNA Hybrid Structures
Richard T. Wheelhouse and Jonathan B. Chaires
5. Quantification of Binding Data Using Capillary Electrophoresis
Fitsumbirhan Araya, Graham G. Skellern, and Roger D. Waigh
6. Determination of Equilibrium Association Constants of Ligand-DNA Complexes by Electrospray Mass Spectrometry
Valérie Gabelica
7. Detection of Adriamycin-DNA Adducts by Accelerator Mass Spectrometry
Kate Coldwell, Suzanne M. Cutts, Ted J. Ognibene, Paul T. Henderson, and Don R. Phillips
8. Molecular Modelling Methods to Quantitate Drug-DNA Interactions
Hao Wang and Charles A. Laughton
9. Application of Anomalous Diffraction Methods to the Study of DNA and DNA-Complexes
Derrick Watkins, Tinoush Moulaei, Seiji Komeda, and Loren Dean Williams
10. DNase I Footprinting.
Antonia S. Cardew and Keith R. Fox
11. Methods to Characterize the Effect of DNA-Modifying Compounds on Nucleosomal DNA
Vidya Subramanian, Robert M. Williams, Dale L. Boger, and Karolin Luger
12. REPSA: Combinatorial Approach for Identifying Preferred Drug-DNA Binding Sequences
Michael W. Van Dyke
13. In Vitro Transcription Assay for Resolution of Drug-DNA Interactions at Defined DNA Sequences
Benny J. Evison, Don R. Phillips, and Suzanne M.Cutts
14. In Vitro Footprinting of Promoter Regions within Supercoiled Plasmid DNA
Daekyu Sun
15. Topoisomerase I-Mediated DNA Relaxation as a Tool to Study Intercalation of Small Molecules into Supercoiled DNA
Paul Peixoto, Christian Bailly, and Marie-Hélene David-Cordonnier
16. A High-Throughput Assay for DNA Topoisomerases and Other Enzymes, Based on DNA Triplex Formation.
Matthew R. Burrell, Nicolas P. Burton, and Anthony Maxwell
17. Measurement of DNA Interstrand Crosslinking in Individual Cells Using the Single Cell Gel Electrophoresis (Comet) Assay
Victoria J. Spanswick, Janet M. Hartley, and John A. Hartley
18. Measurement of DNA Interstrand Crosslinking in Naked DNA Using Gel-Based Methods
Konstantinos Kiakos, Janet M. Hartley, and John A. Hartley
19. An Evaluation Cascade for G-Quadruplex Telomere Targeting Agents in Human Cancer Cells
Mekala Gunaratnam and Stephen Neidle