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The rationale for the design of structural analogues of a normal metabolite is that such compounds may interfere in the utilization or function of the metabolite. A compound which is effective in this respect may be called an antimetabolite. To be successful in chemotherapy of bacterial, viral, or tumor growth, an antimetabolite should adversely affect some vital metabolic reactions in the parasite or parasitic tissue without seriously endangering the host tissue. If a metabolic process of the offending growth is different from that of the host, it is likely that the metabolism or activity of a compound, structurally related to a metabolite involved in that process, will also be different in these cells. Such differences are useful for devising effective drugs with selective actions. Sulfanilamide, a structural analogue of para aminobenzoic acid, interferes with the utilization of this metabolite in the synthesis of folic acid, an essential factor for growth. Bacteria synthesize their own folic acid and are incapable of utilizing exogenously available folic acid. However, the situation is exactly opposite in the animal host. That is, animal tissues cannot synthesize folic acid and are absolutely dependent upon exogenous sources. These differences in metabolism make possible the use of sulfanilamide as a selective inhibitor of growth. Other antibacterial or antiparasitic drugs, such as penicillin (BURCHALL, FERONE and HITCHINGS, 1965) and inhibitors of dihydrofolate reductase (HITCHINGS and BURCHALL, 1965; HITCHINGS, 1964; BURCHALL and HITCHINGS, 1965) have analogous desirable selective toxicity effects.
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.
A review of innovative tools for creative nucleic acid chemists that open the door to novel probes and therapeutic agents Nucleic acids continue to gain importance as novel diagnostic and therapeutic agents. With contributions from noted scientists and scholars, Enzymatic and Chemical Synthesis of Nucleic Acid Derivatives is a practical reference that includes a wide range of approaches for the synthesis of designer nucleic acids and their derivatives. The book covers enzymatic (including chemo-enzymatic) methods, with a focus on the synthesis and incorporation of modified nucleosides. The authors also offer a review of innovative approaches for the non-enzymatic chemical synthesis of nucleic acids and their analogs and derivatives, highlighting especially challenging species. The book offers a concise review of the methods that prepare novel and heavily modified polynucleotides in sufficient amount and purity for most clinical and research applications. This important book: -Presents a timely and topical guide to the synthesis of designer nucleic acids and their derivatives -Addresses the growing market for nucleotide-derived pharmaceuticals used as anti-infectives and chemotherapeutic agents, as well as fungicides and other agrochemicals. -Covers novel methods and the most recent trends in the field -Contains contributions from an international panel of noted scientistics Written for biochemists, medicinal chemists, natural products chemists, organic chemists, and biotechnologists, Enzymatic and Chemical Synthesis of Nucleic Acid Derivatives is a practice-oriented guide that reviews innovative methods for the enzymatic as well as non-enzymatic synthesis of nucleic acid species.
While adenosine triphosphate (ATP) is described as the universal currency of energy in all living organisms at the cellular level, the actual power lies in its phosphate tail. This book is the first dedicated to the field of nucleoside triphosphate (NTP). Its 13 chapters encompass the contributions of twenty scientists from both academia and industry. It provides collective information on the chemical, physiochemical, and biological properties of both natural and modified NTP and their application in life sciences. Three chapters review families of enzymes that depend on nucleotides for assembling DNA and RNA molecules. The appendix includes supporting NMR data.
Spherical nucleic acids (SNAs) comprise a nanoparticle core and a densely packed and highly oriented nucleic acid shell, typically DNA or RNA. They have novel architecture-dependent properties that distinguish them from all other forms of nucleic acids and make them useful in materials synthesis, catalysis, diagnostics, therapeutics, and optics/plasmonics. This book covers over two decades of Dr. Mirkin’s research on SNAs and their anisotropic analogues, including synthesis and fundamental properties, and applications in colloidal crystallization, adaptive matter, and nanomedicine, spanning extra- and intracellular diagnostics, gene regulation, and immunomodulation. It is a reprint volume that compiles 101 key papers from high-impact journals in this research area published by the Mirkin Group at Northwestern University, Illinois, USA, within the International Institute for Nanotechnology, and collaborators. Volume 1 provides an overview and a historical framework of engineering matter from DNA-modified constructs and discusses the enabling features of nucleic acid–functionalized nanomaterials. Volume 2 covers design rules for colloidal crystallization, building blocks for crystal engineering, and DNA and RNA as programmable bonds. Volume 3 discusses colloidal crystallization processes and routes to hierarchical assembly, dynamic nanoparticle superlattices, surface-based and template-confined colloidal crystallization, optics and plasmonics with nanoparticle superlattices, and postsynthetic modification and catalysis with nanoparticle superlattices. Volume 4 covers diagnostic modalities, and intracellular therapeutic and diagnostic schemes based upon nucleic acid–functionalized nanomaterials.
The structure, function and reactions of nucleic acids are central to molecular biology and are crucial for the understanding of complex biological processes involved. Revised and updated Nucleic Acids in Chemistry and Biology 3rd Edition discusses in detail, both the chemistry and biology of nucleic acids and brings RNA into parity with DNA. Written by leading experts, with extensive teaching experience, this new edition provides some updated and expanded coverage of nucleic acid chemistry, reactions and interactions with proteins and drugs. A brief history of the discovery of nucleic acids is followed by a molecularly based introduction to the structure and biological roles of DNA and RNA. Key chapters are devoted to the chemical synthesis of nucleosides and nucleotides, oligonucleotides and their analogues and to analytical techniques applied to nucleic acids. The text is supported by an extensive list of references, making it a definitive reference source. This authoritative book presents topics in an integrated manner and readable style. It is ideal for graduate and undergraduates students of chemistry and biochemistry, as well as new researchers to the field.
How small can a free-living organism be? On the surface, this question is straightforward-in principle, the smallest cells can be identified and measured. But understanding what factors determine this lower limit, and addressing the host of other questions that follow on from this knowledge, require a fundamental understanding of the chemistry and ecology of cellular life. The recent report of evidence for life in a martian meteorite and the prospect of searching for biological signatures in intelligently chosen samples from Mars and elsewhere bring a new immediacy to such questions. How do we recognize the morphological or chemical remnants of life in rocks deposited 4 billion years ago on another planet? Are the empirical limits on cell size identified by observation on Earth applicable to life wherever it may occur, or is minimum size a function of the particular chemistry of an individual planetary surface? These questions formed the focus of a workshop on the size limits of very small organisms, organized by the Steering .Group for the Workshop on Size Limits of Very Small Microorganisms and held on October 22 and 23, 1998. Eighteen invited panelists, representing fields ranging from cell biology and molecular genetics to paleontology and mineralogy, joined with an almost equal number of other participants in a wide-ranging exploration of minimum cell size and the challenge of interpreting micro- and nano-scale features of sedimentary rocks found on Earth or elsewhere in the solar system. This document contains the proceedings of that workshop. It includes position papers presented by the individual panelists, arranged by panel, along with a summary, for each of the four sessions, of extensive roundtable discussions that involved the panelists as well as other workshop participants.
The field of genetics is rapidly evolving and new medical breakthroughs are occurring as a result of advances in knowledge of genetics. This series continually publishes important reviews of the broadest interest to geneticists and their colleagues in affiliated disciplines.
Advanced Topics in Forensic DNA Typing: Interpretation builds upon the previous two editions of John Butler's internationally acclaimed Forensic DNA Typing textbook with forensic DNA analysts as its primary audience. Intended as a third-edition companion to the Fundamentals of Forensic DNA Typing volume published in 2010 and Advanced Topics in Forensic DNA Typing: Methodology published in 2012, this book contains 16 chapters with 4 appendices providing up-to-date coverage of essential topics in this important field. Over 80 % of the content of this book is new compared to previous editions. - Provides forensic DNA analysts coverage of the crucial topic of DNA mixture interpretation and statistical analysis of DNA evidence - Worked mixture examples illustrate the impact of different statistical approaches for reporting results - Includes allele frequencies for 24 commonly used autosomal STR loci, the revised Quality Assurance Standards which went into effect September 2011
An essential guide that puts the focus on method developments and applications in aptamers In recent years, aptamer-based systems have been developed for a wide-range of analytical and medical applications. Aptamers for Analytical Applications offers an introduction to the topic, outlines the common protocols for aptamer synthesis, as well as providing information on the different optimization strategies that can obtain higher affinities to target molecules. The contributors?noted experts on the topic?provide an in-depth review of the characterization of aptamer-target molecule interaction and immobilization strategies and discuss the developments of methods for all the relevant applications. The book outlines different schemes to efficiently immobilize aptamers on substrates as well as summarizing the characterization methods for aptamer-ligand complexes. In addition, aptamer-based colorimetric, enzyme-linked, fluorescent, electrochemical, lateral flow and non-labeling analytical methods are presented. The book also reflects state-of-the-art and emerging applications of aptamer-based methods. This important resource: -Provides a guide to aptamers which provide highly specific and sensitive molecular recognition, with affinities in the range of antibodies and are much cheaper to produce -Offers a discussion of the analytical method developments and improvements with established systems and beyond -Offers a comprehensive guide to all the relevant application areas -Presents an authoritative book from contributors who are noted experts in the field Written for analytical chemists, biochemists, analytical researchers, Aptamers for Analytical Applications is a comprehensive book that adopts a methodological point of view to the important aspects of aptamer generation and modification with a strong emphasis on method developments for relevant applications.