Methods for Studying Nucleic Acid/Drug Interactions

Methods for Studying Nucleic Acid/Drug Interactions

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Features

  • Inspires young scientists to continue the advancement of these methods in light of current capabilities for assay miniaturization and enhanced sensitivity using microfluidics and nanomaterials
  • Surveys possible future techniques as well as highlights their drawbacks and advantages with respect to commonly used tools
  • Introduces several classical techniques, including crystallography, NMR and mass spectroscopy, optical, and calorimetry-based techniques
  • Details diverse aspects of powerful fluorescence-based techniques, electrospray mass spectrometry (ESI-MS) techniques, electrophoresis-based techniques, surface plasmon resonance (SPR) detection, continuous wave (CW) EP, computational modeling, and microarray-based methods
  • Reports on the use of optical tweezers, atomic force microscopy (AFM), and the use of nanopores as ion microscopes that scan individual nucleic acids and detect ligand binding
  • Discusses theoretical developments useful for analyzing and interpreting experimental data, including chemical kinetics, a theoretical perspective on DNA/drug interactions and a wide array of molecular dynamics studies that investigate the interactions of various ligands with nucleic acids

Summary

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.

Table of Contents

CLASSICAL TECHNIQUES
Using Spectroscopic Techniques to Examine Drug-DNA Interactions
Spectroscopic Methods of Analysis

Probing DNA and RNA Interactions with Biogenic and Synthetic Polyamines: Models and Biological Implications
Analytical methods used for structural analysis of polyamine-nucleic acid complexes

EMERGING TECHNIQUES
Mass Spectrometry-Based Techniques for Studying Nucleic Acid/Small Molecule Interactions
Basics of ESI-MS Screening and Detection

Real-Time Monitoring of Nucleic Acid Interactions with Biosensor-Surface Plasmon Resonance
Basic components and steps in a biosensor-SPR experiment

Studying Aptamer/Ligand Interactions Using Fluorescence Correlation Spectroscopy
Basics of fluorescence correlation spectroscopy

Studying Nucleic Acid - Drug Interactions at the Single Molecule Level Using Optical Tweezers

Fluorescent Nucleoside Analogues for Monitoring RNA–Drug Interactions
Basics of Fluorescence Spectroscopy

Atomic Force Microscopy Investigation of DNA-Drug Interactions
Basics of AFM for biomedical research

Characterizing RNA-Ligand Interactions Using 2-Dimensional Combinatorial Screening

EPR Spectroscopy for the Study of RNA-Ligand Interactions
Case studies: Structural dynamics of the TAR RNA

Electrochemical Approaches to the Study of DNA-Drug Interactions

Nanopore Ion Microscope for Detecting Nucleic Acid/Drug Interactions
Basics of Nanopore Sensing

A Primer for Relaxation Kinetic Measurements
Case Studies: Binding to Nucleic Acids and Statistically Excluded Site Binding

DNA-Drug Interactions: A Theoretical Perspective

Computational Studies of RNA Dynamics and RNA-Ligand Interactions
Simulating RNA and its complexes with small molecules

All chapters include case studies, background and basics, prospects and outlook, conclusions, and references

Editor Bio(s)

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.

Editorial Reviews

"By focusing on a selection of novel and emerging techniques, Wanunu and Tor provide a remarkable overview of biophysical and computational advances in structure-based investigations of the interactions between nucleic acids and small-molecule ligands. An impressive collection of approaches is described: analytical biophysical techniques alongside novel exploitation of chemical and computational tools. Indeed, the smart combination of results obtained by classical methods with state of the art biophysical approaches reveals astonishing insights, thus paving new research avenues in this central area of research."
—Prof. Ada Yonath, Weizmann Institute of Science, 2009 Nobel Laureate in Chemistry

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