Download or read book Effect of Small Molecules on Nucleic Acid Stability and Improvements to RNA Structure Prediction written by Kehinde Sowunmi and published by GRIN Verlag. This book was released on 2020-07-14 with total page 32 pages. Available in PDF, EPUB and Kindle. Book excerpt: Academic Paper from the year 2020 in the subject Biology - Genetics / Gene Technology, grade: 9.0, , course: Cell Biology and Genetics, language: English, abstract: Nucleic acids have proven to be viable targets for small molecule drugs. While many examples of such drugs are detailed in the literature, only a select few have found practical use in a clinical setting. These currently employed nucleic acid targeting therapies suffer from either debilitating off-target side effects or succumb to a resistance mechanism of the target. The need for new small molecules that target nucleic acids is evident. However, designing a novel drug to bind to DNA or RNA requires a detailed understanding of exactly what binding environments each nucleic acid presents. In an effort to broaden this knowledge, the work presented in this thesis details the binding location and affinity of known and novel nucleic acid binding small molecules with targets ranging from simple RNA secondary structure all the way to the complex structure of ribosomal RNA. Specifically, it is shown that the anthracycline classes of antineoplastics prefer to bind at or near mismatch base pairs in both physiologically relevant iron responsive element RNA hairpin constructs as well as DNA hairpin constructs presenting mismatched base pairs. Also characterized in this thesis is a novel class of topoisomerase II / histone deacetylase inhibitor conjugates that display a unique affinity for DNA over RNA. Finally, the novel class of macrolide-peptide conjugates, known as peptolides, is shown to retain potent translation inhibition of the prokaryotic ribosome and identification of a novel binding site for the anthracycline class of drugs and the characterization of the two novel drug designs presented in this thesis will undoubtedly aid in the effort to design and discover new molecules that aim for nucleic acid targets.

Download or read book Small Molecule DNA and RNA Binders written by Martine Demeunynck and published by John Wiley & Sons. This book was released on 2006-03-06 with total page 754 pages. Available in PDF, EPUB and Kindle. Book excerpt: The development of molecules that selectively bind to nucleic acids has provided many details about DNA and RNA recognition. The range of such substances, such as metal complexes, peptides, oligonucleotides and a wide array of synthetic organic compounds, is as manifold as the functions of nucleic acids. Nucleic acid recognition sequences are often found in the major or minor groove of a double strand, while other typical interactions include intercalation between base pairs or the formation of triple or quadruple helices. One example of a binding mode that has recently been proposed is end stacking on such complex structures as the telomere tetraplex. In this comprehensive book, internationally recognized experts describe in detail the important aspects of nucleic acid binding, and in so doing present impressive approaches to drug design. Since typical substances may be created naturally or synthetically, emphasis is placed on natural products, chemical synthesis, the use of combinatorial libraries, and structural characterization. The whole is rounded off by contributions on molecular modeling, as well as investigations into the way in which any given drug interacts with its nucleic acid recognition site.

Download or read book Interaction of Small Molecules with Nucleic Acid Targets written by Joshua Craig Canzoneri and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Nucleic acids have proven to be viable targets for small molecule drugs. While many examples of such drugs are detailed in the literature, only a select few have found practical use in a clinical setting. These currently employed nucleic acid targeting therapies suffer from either debilitating off-target side effects or succumb to a resistance mechanism of the target. The need for new small molecules that target nucleic acids is evident. However, designing a novel drug to bind to DNA or RNA requires a detailed understanding of exactly what binding environments each nucleic acid presents. In an effort to broaden this knowledge, the work presented in this thesis details the binding location and affinity of known and novel nucleic acid binding small molecules with targets ranging from simple RNA secondary structure all the way to the complex structure of ribosomal RNA. Specifically, it is shown that the anthracycline class of antineoplastics prefer to bind at or near mismatch base pairs in both physiologically relevant iron responsive element RNA hairpin constructs as well as DNA hairpin constructs presenting mismatched base pairs. Also characterized in this thesis is a novel class of topoisomerase II / histone deacetylase inhibitor conjugates that display a unique affinity for DNA over RNA. Finally, the novel class of macrolide-peptide conjugates, known as peptolides, are shown to retain potent translation inhibition of the prokaryotic ribosome. The binding pocket of the peptolides, including a crevice previously unreachable by macrolides that extends away from the peptidyl transferase center toward the subunit interface, is confirmed in detail via chemical footprinting of the 70S ribosome. Overall, the identification of a novel binding site for the anthracycline class of drugs and the characterization of the two novel drug designs presented in this thesis will undoubtedly aid in the effort to design and discover new molecules that aim for nucleic acid targets. For example, the anthracycline derivative topoisomerase II / histone deacetylase inhibitor conjugates, with their differential mode of nucleic acid binding, may prove to have a unique side effect profile in a therapeutic application. The peptolide compounds also have the potential to be applied as novel antibiotics as they bind to an area of the prokaryotic ribosome unrelated to known macrolide resistance mutations. Furthermore, as a result of the observation of this thesis work that some peptolides also posses eukaryotic translation inhibition capabilities, they could prove to be useful in preventing the growth of rapidly proliferating eukaryotic cells such as plasmodium, leishmania, or tumor cells. Additionally, different head groups could be utilized in creating new peptolides; for example, an oxazolidinone antibiotic could be employed to sample a different binding area of the ribosome.

Download or read book RNA 3D Structure Analysis and Prediction written by Neocles Leontis and published by Springer Science & Business Media. This book was released on 2012-06-05 with total page 402 pages. Available in PDF, EPUB and Kindle. Book excerpt: With the dramatic increase in RNA 3D structure determination in recent years, we now know that RNA molecules are highly structured. Moreover, knowledge of RNA 3D structures has proven crucial for understanding in atomic detail how they carry out their biological functions. Because of the huge number of potentially important RNA molecules in biology, many more than can be studied experimentally, we need theoretical approaches for predicting 3D structures on the basis of sequences alone. This volume provides a comprehensive overview of current progress in the field by leading practitioners employing a variety of methods to model RNA 3D structures by homology, by fragment assembly, and by de novo energy and knowledge-based approaches.

Download or read book Ion Dependent Stability of RNA Three way Junction and DNA Triple Helices written by Gengsheng Chen and published by . This book was released on 2011 with total page 106 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nucleic acids are critical for regulation of gene expression. Because nucleic acid molecules are highly charged, the folding of nucleic acids involves massive charge build-up. The counterions would neutralize the negative charges on nucleic acids and screen the Coulomb repulsion between the different parts of the nucleic acids. Thus, ions can provide a significant stabilizing force in nucleic acid folding. Although considerable progress has been made in the studies of ion electrostatic interaction in nucleic acid folding, the current theoretical models are unable to predict ion effects in nucleic acid folding. One of the key issues that cannot be addressed is the effect of ion correlation, which is significant in Mg2+-nucleic acid interactions. We develop a new model, called the tightly bound ion (TBI) model, to predict ion effects in nucleic acid folding by accounting for the ion correlation effect. Extensive experimental comparisons have shown that, our TBI model can indeed lead to notable improvements in the predictions of the ion-dependent stability of nucleic acids. As an application, we employ the TBI model to investigate the ion-dependent free energy landscape for the RNA three-way junction. The TBI-predicted folding stability agrees quantitatively with the experimental measurements. As a further application of the model, we apply the TBI model to investigate the ion-dependent stability of DNA triple helices. By calculating the free energy landscape of a pair of triple helices immersed in an ionic solution, we first demonstrated divalent ions induced condensation of triple-strand DNA theoretically. Besides, the positive charges on the protonated cytosine residues in the third strand lead to a sequence-dependent electrostatic contribution to triplex stability. We calculated electrostatic free energies for different sequence of triplexes and compared the sequence dependent electrostatic free energy to the experimental measured melting temperature. Our TBI model predicted sequence dependent stability of DNA triplex agrees well with the experimental results.

Download or read book Nucleic Acids written by Victor A. Bloomfield and published by Sterling Publishing Company. This book was released on 2000-04-17 with total page 854 pages. Available in PDF, EPUB and Kindle. Book excerpt: Providing a comprehensive account of the structures and physical chemistry properties of nucleic acids, with special emphasis on biological function, this text has been organized to meet the needs of those who have only a basic understanding of physical chemistry and molecular biology.

Download or read book RNA Structure and Folding written by Dagmar Klostermeier and published by Walter de Gruyter. This book was released on 2013-10-14 with total page 432 pages. Available in PDF, EPUB and Kindle. Book excerpt: While structure-function relationships of proteins have been studied for a long time, structural studies of RNA face additional challenges. Nevertheless, with the continuous discovery of novel RNA molecules with key cellular functions and of novel pathways and interaction networks, the need for structural information of RNA is still increasing. This volume provides an introduction into techniques to assess structure and folding of RNA. Each chapter explains the theoretical background of one technique, and illustrates possibilities and limitations in selected application examples.

Download or read book RNA Sequence Structure and Function Computational and Bioinformatic Methods written by Jan Gorodkin and published by Humana. This book was released on 2014-03-18 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The existence of genes for RNA molecules not coding for proteins (ncRNAs) has been recognized since the 1950's, but until recently, aside from the critically important ribosomal and transfer RNA genes, most focus has been on protein coding genes. However, a long series of striking discoveries, from RNA's ability to carry out catalytic function, to discovery of riboswitches, microRNAs and other ribo-regulators performing critical tasks in essentially all living organisms, has created a burgeoning interest in this primordial component of the biosphere. However, the structural characteristics and evolutionary constraints on RNA molecules are very different from those of proteins, necessitating development of a completely new suite of informatic tools to address these challenges. In RNA Sequence, Structure, Function: Computational and Bioinformatic Methods, expert researchers in the field describe a substantial and relevant fraction of these methodologies from both practical and computational/algorithmic perspectives. Focusing on both of these directions addresses both the biologist interested in knowing more about RNA bioinformatics as well as the bioinformaticist interested in more detailed aspects of the algorithms. Written in the highly successful Methods in Molecular Biology series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results. Thorough and intuitive, RNA Sequence, Structure, Function: Computational and Bioinformatic Methods aids scientists in continuing to study key methods and principles of RNA bioinformatics.

Download or read book Targeting Unique Nucleic Acid Structures with Small Molecules written by Victor Kin-man Tam and published by . This book was released on 2007 with total page 217 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book RNA Mapping written by M. Lucrecia Alvarez and published by Humana Press. This book was released on 2014-07-24 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: In RNA Mapping- Methods and Protocols expert researchers in the field detail many of the methods which are now commonly used to study RNA. These include protocols for the consequence of the emerging interest in the characterization of cellular RNAs urged by their potential use as diagnostic biomarkers or therapeutic targets. In particular, the biological relevance of microRNAs in human physiology and disease development is highlighted in the 16 chapters focused on methods for their physical and functional mapping. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, RNA Mapping- Methods and Protocols provides instruction and inspiration for scientists who are facing the challenges of the discovery and/or functional characterization of RNA molecules for a wide variety of applications ranging from novel biomedical diagnostics to therapeutics and biomaterials.

Download or read book Analysis and Effect of Small molecules Targeting Pre microRNA Structures and Synthetic Efforts Toward a Novel Scaffold for RNA Targeting written by Oliver Leonard Rayborn Swart and published by . This book was released on 2019 with total page 176 pages. Available in PDF, EPUB and Kindle. Book excerpt: "The growing understanding of functional non-coding RNA has seen a sharp rise in the importance of RNA both as a player in functional biology and for its role in the manifestation of many types of disease. This has stimulated the need for design and discovery of small molecules that can specifically interact with RNAs, for use as chemical probes and therapeutics. However, there is difficulty in the production of these molecules as the "rules" which govern the specific RNA interactions are not fully understood. This thesis discusses the application of a resin-bound dynamic combinatorial library (RBDCL) in the discovery of molecules which possess affinity and specificity toward unique RNA structures, as well as the modification and analysis of such molecules as RNA ligands in vitro and in celluo. Moreover, a novel RNA-focused small molecule library is proposed, centered about the use of a 2,5-diketopiperazine (DKP) chemical scaffold. Synthetic routes to this structure and their utility in exploring chemical diversity are discussed. Toward the utility of an RBDCL in evolving RNA binding molecules, an approach was carried out using the premature forms of microRNAs 21 and 96 as targets for small molecule interaction. In their mature states, both of these RNAs function as oncogenes in many forms of cancer. Derived molecules demonstrate ability to bind preferentially to a specific premature structure with strong affinities. Enzymatic studies performed in vitro elucidate the utility of the molecules binding modes in preventing the generation of the mature RNAs at low micromolar concentrations. In cancer cell cultures, treatment with these molecules corresponds to increases in apoptotic events, suggesting reinstated tumor suppressor function through microRNA inhibition. Apoptosis observed with treatment also displays an additive effect when treated with cell death related cytokines or chemotherapeutics. Heterocyclic substructures, particularly those with rod-like orienting ability, have displayed a high degree of utility in the generation of RNA-preferenced small molecules. The 2,5-diketopiperazaine is a synthetically simple heterocycle with a notable pedigree in biologically active molecules. Surprisingly, this molecular scaffold has as yet never been targeted to RNA structure interaction. Synthetic pathways to differentially substituted DKPs are explored both in solution and on solid-phase for application to a dynamic library. Analysis of the RNA interacting capability of the DKP scaffold was performed through the use of a previously known RNA-binding molecule. A mono-quinoline analogue containing a DKP structure was able to bind the HIV-1 frameshift stimulatory sequence of RNA with affinity comparable to the non-DKP molecules despite the loss of a quinoline heterocycle. This is the first instance demonstrating a 2,5-diketopiperazine containing molecule participating in RNA binding"--Pages viii-ix.

Download or read book Protein Nucleic Acid Interactions written by Phoebe A. Rice and published by Royal Society of Chemistry. This book was released on 2008-05-22 with total page 417 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides both in-depth background and up-to-date information in this area. The chapters are organized by general themes and principles, written by experts who illustrate topics with current findings. Topics covered include: - the role of ions and hydration in protein-nucleic acid interactions - transcription factors and combinatorial specificity - indirect readout of DNA sequence - single-stranded nucleic acid binding proteins - nucleic acid junctions and proteins, - RNA protein recognition - recognition of DNA damage. It will be a key reference for both advanced students and established scientists wishing to broaden their horizons.

Download or read book Circular Dichroism and the Conformational Analysis of Biomolecules written by G.D. Fasman and published by Springer Science & Business Media. This book was released on 2013-11-11 with total page 739 pages. Available in PDF, EPUB and Kindle. Book excerpt: ''Excellent and very timely....It will undoubtedly become a standard reference for the application of circular dichroism (CD) to biomolecules.'' --- Quarterly Review of Biology, March 1997 ''[T]estament to the book's utility is the fact that during the course of my review I had to 'rescue' it from the desks of graduate students on an almost daily basis. In summary, this is a great book.'' --- American Scientist ''Well documented chapters provide a very good insight into the problems surrounding the conformation of biomacromolecules...An indispensible source of information.'' --- Nahrung, 42(2), 1998 Renowned experts present the first state-of-the-art description of circular dichroism spectroscopy (CD). Chapters present in-depth discussions of the history of the field, the theory of CD for application to globular proteins, membrane proteins, peptides, nucleic acids and their interactions, carbohydrates, and instrumentation. Discussions also feature new techniques using synchrotron radiation, vibrational Raman optical activity, and vibrational CD. More than 250 illustrations supplement the text.

Download or read book Research Awards Index written by and published by . This book was released on 1988 with total page 874 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book The RNA World written by Raymond F. Gesteland and published by . This book was released on 1999 with total page 744 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book The Rna World Third Edition written by Gesteland and published by . This book was released on 2006-01-01 with total page 768 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent studies on the activities of RNA in the cell have revolutionized our understanding of the many roles played by this molecule. The first two editions of The RNA World (1993, 1999) shed light on the pre biotic era dominated by this versatile molecule, and provided an overview of the state of RNA research at the time. The new third edition of The RNA World updates this perspective, describing the vast array of newly discovered roles for RNA in the modern world. The updated original chapters are supplemented with new chapters on RNA protein complexes, snRNPs and snoRNPs, telomerase RNA, RNAi, microRNAs, noncoding RNA, and many other subjects. This book is essential reading for anyone interested in the biology of nucleic acids and gene regulation and a valuable resource for teaching these concepts

Download or read book Bioinformatics written by Andreas D. Baxevanis and published by John Wiley & Sons. This book was released on 2020-05-12 with total page 646 pages. Available in PDF, EPUB and Kindle. Book excerpt: Praise for the third edition of Bioinformatics "This book is a gem to read and use in practice." —Briefings in Bioinformatics "This volume has a distinctive, special value as it offers an unrivalled level of details and unique expert insights from the leading computational biologists, including the very creators of popular bioinformatics tools." —ChemBioChem "A valuable survey of this fascinating field. . . I found it to be the most useful book on bioinformatics that I have seen and recommend it very highly." —American Society for Microbiology News "This should be on the bookshelf of every molecular biologist." —The Quarterly Review of Biolog" The field of bioinformatics is advancing at a remarkable rate. With the development of new analytical techniques that make use of the latest advances in machine learning and data science, today’s biologists are gaining fantastic new insights into the natural world’s most complex systems. These rapidly progressing innovations can, however, be difficult to keep pace with. The expanded fourth edition of the best-selling Bioinformatics aims to remedy this by providing students and professionals alike with a comprehensive survey of the current field. Revised to reflect recent advances in computational biology, it offers practical instruction on the gathering, analysis, and interpretation of data, as well as explanations of the most powerful algorithms presently used for biological discovery. Bioinformatics, Fourth Edition offers the most readable, up-to-date, and thorough introduction to the field for biologists at all levels, covering both key concepts that have stood the test of time and the new and important developments driving this fast-moving discipline forwards. This new edition features: New chapters on metabolomics, population genetics, metagenomics and microbial community analysis, and translational bioinformatics A thorough treatment of statistical methods as applied to biological data Special topic boxes and appendices highlighting experimental strategies and advanced concepts Annotated reference lists, comprehensive lists of relevant web resources, and an extensive glossary of commonly used terms in bioinformatics, genomics, and proteomics Bioinformatics is an indispensable companion for researchers, instructors, and students of all levels in molecular biology and computational biology, as well as investigators involved in genomics, clinical research, proteomics, and related fields.