Drug-DNA Interaction Protocols

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, 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-Hélène 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