Chemical Biology Of The Genome

Chemical Biology of the Genome provides a comprehensive overview of essential concepts and principles of genomic and epigenomics dynamics as explored through the lens of chemical biology. Key examples and case studies illustrate chemical biology methods for study and analysis of the genome and epigenome, with an emphasis on relevance to physiological and pathophysiological processes and drug discovery. Authors and international leaders in biochemical studies of the genome, Drs. Siddhartha Roy and Tapas Kundu, adopt an integrated, interdisciplinary approach throughout, demonstrating how fast evolving chemical and mass-scale sequencing tools are increasingly used to interpret biochemical processes of the genome. Later sections discuss chemical modifications of the genome, DNA sequence recognition by proteins and gene regulation, GWAS and EpiGWAS studies, 3D architecture of the genome, and functional genome architecture. In-depth, discovery focused chapters examine intervention in gene networks using SiRNA/ShRNA, miRNA, and anti-miR, small molecule modulation of iPS, drug resistance pathways altered DNA methylation as drug targets, anti-miR as therapeutics, and nanodelivery of drugs. Offers an interdisciplinary discussion of the chemical biology of the genome and epigenome, employing illustrative case studies in both physiological and pathophysiological contexts Supports researchers in employing chemical and mass-scale sequencing approaches to interpret genomic and epigenomic dynamics Highlights innovative pathways and molecular targets for new disease study and drug discovery

This book focuses on an “outside the box” notion by utilizing the powerful applications of next-generation sequencing (NGS) technologies in the interface of chemistry and biology. In personalized medicine, developing small molecules targeting a specific genomic sequence is an attractive goal. N-methylpyrrole (P)–N-methylimidazole (I) polyamides (PIPs) are a class of small molecule that can bind to the DNA minor groove. First, a cost-effective NGS (ion torrent platform)-based Bind-n-Seq was developed to identify the binding specificity of PIP conjugates in a randomized DNA library. Their biological influences rely primarily on selective DNA binding affinity, so it is important to analyze their genome-wide binding preferences. However, it is demanding to enrich specifically the small-molecule-bound DNA without chemical cross-linking or covalent binding in chromatinized genomes. Herein is described a method that was developed using high-throughput sequencing to map the differential binding sites and relative enriched regions of non-cross-linked SAHA-PIPs throughout the complex human genome. SAHA-PIPs binding motifs were identified and the genome-level mapping of SAHA-PIPs-enriched regions provided evidence for the differential activation of the gene network. A method using high-throughput sequencing to map the binding sites and relative enriched regions of alkylating PIP throughout the human genome was also developed. The genome-level mapping of alkylating the PIP-enriched region and the binding sites on the human genome identifies significant genomic targets of breast cancer. It is anticipated that this pioneering low-cost, high through-put investigation at the sequence-specific level will be helpful in understanding the binding specificity of various DNA-binding small molecules, which in turn will be beneficial for the development of small-molecule-based drugs targeting a genome-level sequence.

Advances in chemistry, biology and genomics coupled with laboratory automation and computational technologies have led to the rapid emergence of the multidisciplinary field of chemical genomics. This edited text, with contributions from experts in the field, discusses the new techniques and applications that help further the study of chemical genomics. The beginning chapters provide an overview of the basic principles of chemical biology and chemical genomics. This is followed by a technical section that describes the sources of small-molecule chemicals; the basics of high-throughput screening technologies; and various bioassays for biochemical-, cellular- and organism-based screens. The final chapters connect the chemical genomics field with personalized medicine and the druggable genome for future discovery of new therapeutics. This book will be valuable to researchers, professionals and graduate students in many fields, including biology, biomedicine and chemistry.

Advanced Chemical Biology The modern approach to teaching chemical biology Advanced Chemical Biology is organized around the central dogma of life, progressing from genes to proteins and higher-order cellular structures, including core application areas such as imaging, chemical genetics, activity-based protein profiling, and natural product discovery and biosynthesis. Advanced topics and applications in, e. g., microbiology, developmental biology, and neurobiology, are covered in separate sections. Every chapter is homogeneous in style and layout, consisting of a short historical introduction followed by a description of the underlying concepts and a selection of recent examples of how the concept has been turned into practice. The subdivision of the contents into core and supplemental chapters enables a flexible use in teaching, both for a one-semester and a two-semester course. Written by authors and editors coming from the leading scientific institutions that have developed the concepts and technologies for this discipline, Advanced Chemical Biology includes specific information on topics like: DNA function, synthesis and engineering, chemical approaches to genome integrity, and RNA function, synthesis, and probing Chemical approaches to transcription and RNA regulation in vivo, chemical biology of genome engineering, and peptide/protein synthesis and engineering Directed evolution for chemical biology, chemical biology of cellular metabolism, chemical biology of lipids, and protein post-translational modifications Chemical glycobiology, chemical and enzymatic modification of proteins, genetic code expansion, bio-orthogonal chemistry, and cellular imaging With its broad scope and focus on turning concepts into applications, Advanced Chemical Biology is an excellent starting point for anyone entering the field and looking for a guide to the wide range of available methods and strategies that chemical biology has to offer. With a Foreword by Nobel Laureate Carolyn Bertozzi.

This book offers a comprehensive and detailed overview of various aspects of long non-coding RNAs. It discusses their emerging significance in molecular medicine, ranging from human cancers to cardiovascular and metabolic diseases. Transcriptomic studies have demonstrated that the majority of genomes found in complex organisms are expressed in highly dynamic and cell-specific patterns, producing huge numbers of intergenic, antisense and intronic long non-protein-coding RNAs (lncRNAs). Thousands of lncRNAs have been identified, and unlike mRNA, they have no protein-coding capacity. A large repertoire of ncRNAs, actively transcribed from the mammalian genome, control diverse cellular processes, both in terms of development and diseases, through a variety of gene regulatory mechanisms. IncRNAs have emerged as a new paradigm in epigenetic regulation of the genome. Given its scope, the book will be of particular interest to molecular, chemical, cell and developmental biologists, as well as specialists in translational medicine involved in disease-oriented research. It also offers a valuable resource for in silico experts seeking a deeper understanding of lncRNA expression and function through computational analysis of the NGS data.

Chemical Biology of Natural Products This unique, long-awaited volume is designed to address contemporary aspects of natural product chemistry and its influence on biological systems, not solely on human interactions. The subjects covered include discovery, isolation and characterization, biosynthesis, biosynthetic engineering, pharmaceutical, and other applications of these compounds. Each chapter begins with a brief and simple introduction to the subject matter, and then proceeds to guide the reader towards the more contemporary, cutting-edge research in the field, with the contributing authors presenting current examples from their own work in order to exemplify key themes. Topics covered in the text include genome mining, heterologous expression, natural product synthesis, biosynthesis, glycosylation, chemical ecology, and therapeutic applications of natural products, both current and potential.

Chemical genomics is a highly interdisciplinary and very exciting field of research both in academics and in the life sciences industry. The Ernst Schering Research Foundation Workshop 58 was organized to bring together scientific leaders in the field to discuss the implications of chemical genomics for drug discovery. Various aspects of the interface between chemistry and biology are covered in this volume, such as chemogenomics efforts in the pharmaceutical industry, diversity-oriented synthesis, chemogenomic approaches to the study of cell function, screening technologies, and natural products as tools in chemical biology.

This volume contains 29 engrossing chapters contributed by worldwide, leading research groups in the field of chemical biology. Topics include pre-biology; the establishment of the genetic code; isomerization of RNA; damage of nucleobases in RNA; the dynamic structure of nucleic acids and their analogs in DNA replication, extra- and intra-cellular transport; molecular crowding by the use of ionic liquids; new technologies enabling the modification of gene expression via editing of therapeutic genes; the use of riboswitches; the modification of mRNA cap regions; new approaches to detect appropriately modified RNAs with EPR spectroscopy and the use of parallel and high-throughput techniques for the analysis of the structure and new functions of nucleic acids. This volume discusses how chemistry can add new frontiers to the field of nucleic acids in molecular medicine, biotechnology and nanotechnology and is not only an invaluable source of information to chemists, biochemists and life scientists but will also stimulate future research.