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A simple thermal melting experiment may be used to demonstrate the stabilization of a given structure by a ligand (usually a small molecule, sometimes a peptide). Preparation of the sample is straightforward, and the experiment itself requires an inexpensive apparatus. Furthermore, re ...

Surface plasmon resonance (SPR) technology with biosensor surfaces has become a widely-used tool for the study of nucleic acid interactions without any labeling requirements. The method provides simultaneous kinetic and equilibrium characterization of the interactions of b ...

The targeting of telomerase and telomere maintenance in human cancer cells can be achieved by small molecules that induce the 3'single-stranded ends of telomeric DNA to fold up into four-stranded quadruplex structures that inhibit the action of the telomerase enzyme complex. In this chap ...

Many DNA-binding small molecules, typically those with a molecular mass less than 1,000 g/mol, recognize duplex DNA with some degree of sequence specificity. These include drugs used to treat several human diseases, including viral and bacterial infections, malaria, and cancer. Determ ...

Eukaryotic DNA forms a complex with an equal mass of proteins to form chromatin. To fully understand the action of DNA-reactive antitumor antibiotics in the cell, their effect must be studied in a chromatin context. In particular, it is of interest to investigate how the distortion of DNA, in the conte ...

We have developed a rapid, high-throughput assay for measuring the catalytic activity (DNA supercoiling or relaxation) of topoisomerase enzymes that is also capable of monitoring the activity of other enzymes that alter the topology of DNA. The assay utilises intermolecular triplex f ...

Several biochemical and biophysical methods are available to study the intercalation of a small molecule between two consecutive base pairs of DNA. Among them, the topoisomerase I-mediated DNA relaxation assay has proved highly efficient, relatively easy to handle and very informat ...

Polypurine/polypyrimidine (pPu/pPy) tracts, which exist in the promoter regions of many growth-related genes, have been proposed to be very dynamic in their conformation. In this chapter, we describe a detailed protocol for DNase I and S1 nuclease footprinting experiments with superc ...

A major class of anticancer agents in current clinical use exerts its anticancer effects by binding covalently or non-covalently to DNA. A detailed understanding of the nature of these drug-DNA complexes would be expected to lead to better uses of these drugs, and also assist with the design of impr ...

Immunogenicity against therapeutic proteins is a clinical problem in the successful treatment of many diseases and, as such, immunogenicity risk assessment in preclinical setting would be useful to improve safety and efficacy of protein-based therapeutics in the product develo ...

Wound healing is a complex process involving the integrated actions of numerous cell types, soluble mediators, and extracellular matrix (ECM). In this study, phospholipase A2 (PLA2) purified from crotalid snake venom was found to express in vitro bactericidal activity against a group of c ...

CD2 is a cell adhesion molecule that mediates T-cell activation by binding to its ligand CD58 on antigen-presenting cells. Interaction between CD2 and CD58 or leukocyte function-associated antigen-3 (LFA-3) helps to optimize immune recognition facilitating contact between T lymp ...

Mass spectrometry (MS)-based quantitative proteomics plays important roles in drug discovery. In this chapter, we describe a stable isotope labeling technique which employs 4-plex iTRAQ™ isobaric reagents coupled with two-dimensional (2-D) liquid chromatography (LC) and MALD ...

Functional chemicals are very useful tools for molecular biology studies. Due to its small size, large progeny clutch, and embryonic transparency, zebrafish serves as a superb in vivo animal model for chemical compound screens and characterization. During zebrafish embryogenesis, ...

Scientists in the pharmaceutical industry have ready access to samples from animal toxicology studies carefully designed to test the safety characteristics of a steady pipeline of agents advancing toward clinical testing. Applications of toxicogenomics to the evaluation of co ...

Microarray technologies can be used to generate massive amounts of gene expression information as an initial step to decipher the molecular mechanisms of toxicologic changes. Identifying genes whose expression is associated with specific toxic end points is an initial step in predi ...

The generation of high-quality microarray data for toxicogenomics can be affected by the study design and methods used for sample acquisition, preparation, and processing. Bias can be introduced during animal treatment, tissue handling, and sample preparation. Metrics and contro ...

In this chapter, we provide a structured approach to the statistical analysis of toxicogenomic data, from the assessment of data quality to data exploration, gene and pathway level analysis, and finally predictive model building. This type of analysis approach can yield toxicogenomic m ...

Reference databases consisting of large sample numbers and high-dimensional microarray data are now available for the investigation of adverse events in animal model systems such as the rat. This large volume of data, accompanied by appropriate study designs, compound and dose select ...

The failure of drug candidates during clinical trials due to toxicity, especially hepatotoxicity, is an important and continuing problem in the pharmaceutical industry. This chapter explores new predictive toxicogenomics approaches to better understand the hepatotoxic po ...