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First, we describe a strategy for performing ordered multistep synthesis in a single solution. This system makes use of temperature-sensitive variations in DNA secondary structure to orchestrate an ordered multistep synthesis of a triolefin and a tripeptide in a single solution. This methodology provides a faster, higher-yielding route to multistep DNA-templated products and represents a mode of controlling chemical reactivity that is not accessible in traditional flask-based reaction formats.
Author : Robert A. Goodnow, Jr. Publisher : John Wiley & Sons Page : 495 pages File Size : 14,51 MB Release : 2014-04-28 Category : Science ISBN : 1118487680
This book comprehensively describes the development and practice of DNA-encoded library synthesis technology. Together, the chapters detail an approach to drug discovery that offers an attractive addition to the portfolio of existing hit generation technologies such as high-throughput screening, structure-based drug discovery and fragment-based screening. The book: Provides a valuable guide for understanding and applying DNA-encoded combinatorial chemistry Helps chemists generate and screen novel chemical libraries of large size and quality Bridges interdisciplinary areas of DNA-encoded combinatorial chemistry – synthetic and analytical chemistry, molecular biology, informatics, and biochemistry Shows medicinal and pharmaceutical chemists how to efficiently broaden available “chemical space” for drug discovery Provides expert and up-to-date summary of reported literature for DNA-encoded and DNA-directed chemistry technology and methods
Progress in Medicinal Chemistry, Volume 57, provides a review of eclectic developments in medicinal chemistry, with this volume including chapters on the CaSR field, CFTR modulators in cystic fibrosis, macrocycles, VMAT2 inhibitors, and Big Data in Drug Discovery. Provides extended, timely reviews of topics in medicinal chemistry Contains targets and technologies relevant to the discovery of tomorrow’s drugs Presents analyses of successful drug discovery programs
Progress in Medicinal Chemistry, Volume 59, provides a review of eclectic developments in medicinal G139 chemistry. Each chapter is written by an international board of authors, with this release focusing on Small Molecules - Giant Leaps for Immuno-Oncology, Reviewing P2X7, Reviewing ASK1, and Reviewing DNA-encoded libraries. Provides extended, timely reviews of topics in medicinal chemistry Contains targets and technologies relevant to the discovery of tomorrow’s drugs Presents analyses of successful drug discovery programs
DNA polymerases synthesize DNA, the essential biomolecule responsible for encoding the complex information necessary for life, with remarkable efficiency and fidelity. Chemists and biologists have exploited this extraordinary enzyme to develop a wide range of biotechnological tools, including but certainly not limited to PCR and Sanger sequencing. While these landmark applications continue to be relied upon to this day, they represent only a small fraction of the possible uses of these enzymes. Here, I detail my work to expand the scope of the enzymatic synthesis of DNA in two distinct fields. Chapters 2-5 detail efforts to identify replicable candidate unnatural base pairs to expand the genetic alphabet from the natural four base code to an expanded six base code. Using a wide range of techniques, including chemical synthesis, directed evolution of DNA polymerases, and screening based methodologies, the d 5SICS:d MMO2 base pair is identified, resulting in our strongest candidate base pair identified to date. Chapter 6 details the use of an activity based phage display system to identify a DNA polymerase that possesses improved recognition of substrates applicable in next generation sequencing applications.
With extensive coverage of synthesis techniques and applications, this text describes chemical biology techniques which have gained significant impetus during the last five years. It focuses on the methods for obtaining modified and native nucleic acids, and their biological applications. Topics covered include: chemical synthesis of modified RNA expansion of the genetic alphabet in nucleic acids by creating new base pairs chemical biology of DNA replication: probing DNA polymerase selectivity mechanisms with modified nucleotides nucleic-acid-templated chemistry chemical biology of peptide nucleic acids (PNA) the interactions of small molecules with DNA and RNA the architectural modules of folded RNAs genesis and biological applications of locked nucleic acid (LNA) small non-coding RNA in bacteria microRNA-guided gene silencing nucleic acids based therapies innate immune recognition of nucleic acid light-responsive nucleic acids for the spatiotemporal control of biological processes DNA methylation frameworks for programming RNA devices RNA as a catalyst: The Diels-Alderase-Ribozyme evolving an understanding of RNA function by in vitro approaches the chemical biology of aptamers: synthesis and applications nucleic acids as detection tools bacterial riboswitch discovery and analysis The Chemical Biology of Nucleic Acids is an essential compendium of the synthesis of nucleic acids and their biological applications for bioorganic chemists, chemical biologists, medicinal chemists, cell biologists, and molecular biologists.
The first two chapters of this invaluable book trace the developments of the chemistry and macromolecular structures, respectively, of proteins and nuclei acids. Similarly, the introductions to the succeeding chapters review, step by step, the historical landmarks in the topics covered. These include discoveries of biological phosphate esters, nucleotides and nucleotide coenzymes (important in intermediary metabolism), the nature of the genetic material and biological synthesis of proteins, formulation of the problem of the genetic code, and perspectives on bioenergetics.The selected papers illustrate the developments of the chemical synthesis of nucleotides and nucleotide coenzymes of ribo- and deoxy-ribo-polynucleotides (RNA, DNA), of the total synthesis of genes in the laboratory, and principles for gene amplification (PCR). Another major section covers studies of enzymes that degrade nucleic acids, the structure of transfer RNA and its role in protein synthesis, and the author's work on the elucidation of the genetic code. Finally, there are descriptions of the studies on biological membranes and the membrane protein bacteriorhodopsin, a biological proton pump. These studies elucidated the mechanism of proton translocation, which is central to bioenergetics.
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.
In The Aptamer Handbook, leading scientists from academia as well as biotech and pharma companies introduce the revolutionary concept of designing RNA and DNA oligonucleotides with novel functions by in vitro selection. These functions comprise high affinity binding (aptamers), catalytic activity (ribozymes and deoxyribozymes) or combinations of binding and catalytic properties (aptazymes). Basic concepts and technologies describing in detail how these functional oligonucleotides can be identified are presented. Numerous examples demonstrate the versatility of in vitro selected oligonucleotides. Special emphasis has been put on a section that shows the broad applicability of aptamers, e. g. in target validation, for analytics, or as new therapeutics. This first overview in the field is of prime interest for a broad audience of scientists both in academia and in industry who wish to expand their knowledge on the potential of new oligonucleotide functions and their applications.