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This book presents a novel method of synthesizing sequence-specific DNA binding pyrrole–imidazole (Py–Im) polyamides and demonstrates polyamides targeting longer base pairs than those previously reported and their cellular application. It discusses the development of the facile synthetic method of tandem hairpin Py–Im polyamides and the method of visualizing telomeres under mild conditions without harsh denaturation, as well as research resulting in the synthesis not only of previously reported tandem dimer polyamides but also longer tandem trimer and tetramer polyamides. Using fluorescently labeled tandem hairpin Py–Im polyamides targeting a human telomere repetitive sequence, the author successfully stained telomeres in fixed cells without denaturation. These fluorescently labeled tandem tetramer polyamides are able to visualize human telomeres with lower background signals than previous polyamide probes, suggesting that they have higher specificity for telomeres. As such, this book provides insights into recent advance in Py–Im polyamides, particularly the extension of the target sites c
This book presents three types of synthetically cooperative DNA recognizing assemblies, in order to advance the development of programmable DNA-binding pyrrole–imidazole polyamides (PIPs). PIPs represent the best-characterized class of small molecule DNA binders that can be modified to bind with any predetermined DNA sequence and regulate gene expression patterns in a transgene-free and cost-effective manner. PIPs are characterized by their small molecular size, high binding affinity, programmability, sequence selectivity, and moderate cell permeability. In recent years, there have been numerous novel studies on the applications of these biological tools; this research is thoroughly review...
This book provides essential insights into designing a localized DNA circuit to promote the rate of desired hybridization reactions over undesired leak reactions in the bulk solution. The area of dynamic DNA nanotechnology, or DNA circuits, holds great promise as a highly programmable toolbox that can be used in various applications, including molecular computing and biomolecular detection. However, a key bottleneck is the recurring issue of circuit leakage. The assembly of the localized circuit is dynamically driven by the recognition of biomolecules – a different approach from most methods, which are based on a static DNA origami assembly. The design guidelines for individual reaction modules presented here, which focus on minimizing circuit leakage, are established through NUPACK simulation and tested experimentally – which will be useful for researchers interested in adapting the concepts for other contexts. In the closing section, the design concepts are successfully applied to the biomolecular sensing of a broad range of targets including the single nucleotide mutations, proteins, and cell surface receptors.
This book addresses the development of both DNA-sequence-selective and DNA-form-selective ligands, with the aim of creating potential molecular probes and therapeutic agents for non-canonical DNA structure-caused human diseases. Over the past two decades, the structural diversity of DNA forms has been proven to have profound implications in various biological, neurological, and pharmacological events. In response, researchers have since made tremendous efforts to obtain highly active drugs interacting with disease-related non-canonical DNA structures. These drugs, however, have not yet been approved for clinical use. One obstacle impeding their clinical application has to do with selectivity...
The realisation that human, animal, viral and bacterial genomes all contain over-representation of higher-order quadruplex structures in regulatory and other pharmacologically-useful regions, has led to a large number of studies aimed at exploiting this findings for therapeutic and diagnostic purposes. Quadruplex-binding small molecules are starting to be evaluated in human clinical trials. - Provides the authority and expertise of leading contributors from an international board of authors - Presents the latest release in the Annual Reports in Medicinal Chemistry series
Guanine rich DNA has been known for decades to form unusual structures, although their biological relevance was little understood. Recent advances have demonstrated that quadruplex structures can play a role in gene expression and provide opportunities for a new class of anticancer therapeutics. A number of quadruplex-specific proteins have also been discovered. Quadruplex Nucleic Acids discusses all aspects of the fundamentals of quadruplex structures, including their structure in solution and the crystalline state, the kinetics of quadruplex folding, and the role of cations in structure and stability. The biology of quadruplexes and G-rich genomic regions and G-quartets in supramolecular chemistry and nanoscience are also considered. Surveying the current state of knowledge, and with contributions from leading experts, this is the first comprehensive review of this rapidly growing area. Quadruplex Nucleic Acids is ideal for researchers interested in areas related to chemistry, chemical biology, medicinal chemistry, molecular pharmacology, and structural and molecular biology.
Discover the fundamentals and intricacies of a subject at the interface of chemistry and biology with this authoritative resource Chemistry and Biology of Non-canonical Nucleic Acids delivers a comprehensive treatment of the chemistry and biology of non-canonical nucleic acids, including their history, structures, stabilities, properties, and functions. You'll learn about the role of these vital compounds in transcription, translation, regulation, telomeres, helicases, cancers, neurodegenerative diseases, therapeutic applications, nanotechnology, and more. An ideal resource for graduate students, researchers in physical, organic, analytical, and inorganic chemistry will learn about uncommon ...
This book spans diverse aspects of modified nucleic acids, from chemical synthesis and spectroscopy to in vivo applications, and highlights studies on chemical modifications of the backbone and nucleobases. Topics discussed include fluorescent pyrimidine and purine analogs, enzymatic approaches to the preparation of modified nucleic acids, emission and electron paramagnetic resonance (EPR) spectroscopy for studying nucleic acid structure and dynamics, non-covalent binding of low- and high-MW ligands to nucleic acids and the design of unnatural base pairs. This unique book addresses new developments and is designed for graduate level and professional research purposes.
This book discusses major technological advances in the treatment and re-use of wastewater. Its focus is on both novel treatment strategies and the modifications and adaptions of conventional processes to optimize the treatment of a complex variety of pollutants, including organic matter, chemicals and micropollutants in different water resources, as well as the integration of water treatment with bioelectricity production. Written by leading researchers in the field, it will be of interest to a wide range of researchers in both industry and academia.
This volume consolidates the key methods for studying ligand-nucleic acid interactions into a convenient source. Techniques that are examined range from biophysical and chemical approaches to methods rooted in molecular and cell biology.