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.

List of contents

Quantitative Analysis of Small Molecule-Nucleic Acid Interactions with a Biosensor Surface and Surface Plasmon Resonance Detection.- Thermal Melting Studies of Ligand DNA Interactions.- Circular and Linear Dichroism of Drug-DNA Systems.- Drug Binding to DNA?RNA Hybrid Structures.- Quantification of Binding Data Using Capillary Electrophoresis.- Determination of Equilibrium Association Constants of Ligand-DNA Complexes by Electrospray Mass Spectrometry.- Detection of Adriamycin-DNA Adducts by Accelerator Mass Spectrometry.- Molecular Modelling Methods to Quantitate Drug-DNA Interactions.- Application of Anomalous Diffraction Methods to the Study of DNA and DNA-Complexes.- DNase I Footprinting.- Methods to Characterize the Effect of DNA-Modifying Compounds on Nucleosomal DNA.- REPSA: Combinatorial Approach for Identifying Preferred Drug-DNA Binding Sequences.- In vitro Transcription Assay for Resolution of Drug-DNA Interactions at Defined DNA Sequences.- In vitro Footprinting of Promoter Regions Within Supercoiled Plasmid DNA.- Topoisomerase I-Mediated DNA Relaxation as a Tool to Study Intercalation of Small Molecules into Supercoiled DNA.- A High-Throughput Assay for DNA Topoisomerases and Other Enzymes, Based on DNA Triplex Formation.- Measurement of DNA Interstrand Crosslinking in Individual Cells Using the Single Cell Gel Electrophoresis (Comet) Assay.- Measurement of DNA Interstrand Crosslinking in Naked DNA Using Gel-Based Methods.- An Evaluation Cascade for G-Quadruplex Telomere Targeting Agents in Human Cancer Cells.

Summary

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.

Additional text

From the reviews of the second edition:
“Provides authoritative and current information on the binding of new generations of DNA sequence reading compounds … . The intended audience includes postgraduates, postdoctoral workers, and established scientists … . even clinical investigators such as oncologists may find this book quite useful. … This well-illustrated book of chapters written by leading experts will be extremely useful for postgraduates, post-doctoral fellows, established scientists, and some clinicians interested in the field of drug-DNA interactions. … this update will be welcomed by students and justifies replacement.” (Omer Iqbal, Doody’s Review Service, May, 2010)

Report

From the reviews of the second edition:
"Provides authoritative and current information on the binding of new generations of DNA sequence reading compounds ... . The intended audience includes postgraduates, postdoctoral workers, and established scientists ... . even clinical investigators such as oncologists may find this book quite useful. ... This well-illustrated book of chapters written by leading experts will be extremely useful for postgraduates, post-doctoral fellows, established scientists, and some clinicians interested in the field of drug-DNA interactions. ... this update will be welcomed by students and justifies replacement." (Omer Iqbal, Doody's Review Service, May, 2010)

Product details

• Assisted by: Keith Fox (Editor), Keith R. Fox (Editor), Keit R Fox (Editor), Keith R Fox (Editor)
• Publisher: Springer, Berlin
• Languages: English
• Product format: Paperback / Softback
• Released: 18.01.2012
• EAN: 9781617796746
• ISBN: 978-1-61779-674-6
• No. of pages: 311
• Weight: 627 g
• Illustrations: IX, 311 p. 103 illus., 1 illus. in color.
• Series: Methods in Molecular Biology; Methods in Molecular Biology
• Subjects: Natural sciences, medicine, IT, technology > Medicine > Pharmacy; B, Pharmacology, Human Genetics, Biomedical and Life Sciences, Medical Genetics, Pharmacology/Toxicology