Methods for Studying DNA/Drug Interactions

Since most therapeutic efforts have been predominantly focused on pharmaceuticals that target proteins, there is an unmet need to develop drugs that intercept cellular pathways that critically involve nucleic acids. Progress in the discovery of nucleic acid binding drugs naturally relies on the availability of analytical methods that assess the efficacy and nature of interactions between nucleic acids and their putative ligands. This progress can benefit tremendously from new methods that probe nucleic acid/ligand interactions both rapidly and quantitatively.

A variety of novel methods for these studies have emerged in recent years, and Methods for Studying DNA/Drug Interactions highlights new and non-conventional methods for exploring nucleic acid/ligand interactions. Designed to present drug-developing companies with a survey of possible future techniques, the book compares their drawbacks and advantages with respect to commonly used tools. Perhaps more importantly, this book was written to inspire young scientists to continue to advance these methods into fruition, especially in light of current capabilities for assay miniaturization and enhanced sensitivity using microfluidics and nanomaterials.

Optical Tweezers and Single-Molecule Detection of Drug Binding. Magnetic Tweezers and Drug Binding Assays. Fluorescence Correlation Spectroscopy (FCS) for Analyzing Nucleic Acid/Drug Complexes. RNA Fluorescent Base Analogs + Small Molecule Interaction. Profiling Nucleic Acid/Drug Interactions Using Synthetic Pores. Carbon Nanotube-Based Detection of DNA/Drug Complexes. Impedance Sensing of DNA Binding Drugs Using Metal Electrodes. Electrochemical Methods for Studying Nucleic Acid/Small Molecule Interactions. On-bead Assays for Gene Targets. Surface Plasmon Resonance for Detecting DNA/Ligand Interactions. Surface Plasmon Resonance Techniques for Studying RNA/Ligand Interactions. Molecular Modeling of RNA Drug Complexes. Vibrational Spectroscopy of RNA-Drug Complexes. Selection Techniques for Identifying Ligand-Binding RNA Motifs. Modeling and Characterization of G-quadraplex Small-Molecule Binders. Electrostatic Field and Brownian Dynamics Simulations of Cationic Drug Binding to RNA.

Meni Wanunu completed his Ph.D. in 2005 at the Weizmann Institute of Science, where he specialized in supramolecular chemistry, self-assembly, and nanomaterials science. He then carried out a postdoctoral position at Boston University and a research associate position at the University of Pennsylvania, where he developed ultrasensitive synthetic nanopores for nucleic acid analysis at the single-molecule level. Currently, he is an Assistant Professor at the Department of Physics and the Department of Chemistry and Chemical Biology at Northeastern University, Boston. His research interests include developing chemical approaches for investigating biomolecular structure and behavior, nucleic acid mechanics and dynamics, and probing biological processes at the single-molecule level.

Yitzhak Tor carried out his doctorate work at the Weizmann Institute of Science, earning his Ph.D. in 1990. After a postdoctoral stay at the California Institute of Technology (1990–1993), he took his first faculty position at the University of Chicago. In 1994, he moved to the University of California, San Diego, where he is currently a Professor of Chemistry and Biochemistry and the Traylor Scholar in Organic Chemistry. His research interests are diverse and include chemistry and biology of nucleic acids, the discovery of novel antiviral and antibacterial agents, as well as the development of cellular delivery agents and fluorescent probes. He is currently the Editor in Chief of Perspectives in Medicinal Chemistry (http://la-press.com/journal.php?journal_id=25) and Organic Chemistry Insights (http://www.la-press.com/organic-chemistry-insights-journal-j104). Away from chemistry, his interests are predominantly in music, playing, recording and producing his own instrumental CDs.