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 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 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 Selective Targeting of Nucleic Acids by Small Molecules written by Caterina Musetti and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book RNA as a Drug Target written by John Schneekloth and published by John Wiley & Sons. This book was released on 2024-10-07 with total page 418 pages. Available in PDF, EPUB and Kindle. Book excerpt: Discover a new paradigm in drug discovery that greatly expands the space of addressable drug targets and potential novel drugs Existing paradigms for drug discovery have focused largely on enzymes and other proteins as drug targets. In recent years, however, different varieties of ribonucleic acids have emerged as a viable focus for target-based drug discovery, with the potential to revolutionize the strategy and approach for this essential step in the drug development process. RNA as a Drug Target: The Next Frontier for Medicinal Chemistry offers a practice-oriented introduction to developing drug-like small molecules that selectively modulate both coding and non-coding RNAs. Beginning with a description and characterization of existing druggable RNAs, the book discusses how to approach different RNA targets for drug discovery. The result is a crucial resource for targeting RNAs and creating the next generation of life-saving pharmaceuticals. RNA as a Drug Target readers will also find: A complete “toolbox” for working with RNA, from structure determination to screening and lead generation techniques A wide range of addressable targets and mechanisms, including splicing modulation, riboswitches, targeted degradation, and more Authoritative discussion of the potential of RNA-targeted small molecule therapeutics for drugging the epitranscriptome RNA as a Drug Target provides an expert introduction to a new frontier in pharmaceutical research for medicinal chemists, biochemists, molecular biologists, and members of the pharmaceutical industry.
Download or read book Long Non Coding RNA Biology written by M.R.S. Rao and published by Springer. This book was released on 2017-08-16 with total page 336 pages. Available in PDF, EPUB and Kindle. Book excerpt: This contributed volume offers a comprehensive and detailed overview of the various aspects of long non-coding RNAs and discusses their emerging significance. Written by leading experts in the field, it motivates young researchers around the globe, and offers graduate and postgraduate students fascinating insights into genes and their regulation in eukaryotes and higher organisms.
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 DNA targeting Molecules as Therapeutic Agents written by Michael J. Waring and published by Royal Society of Chemistry. This book was released on 2018-03-12 with total page 432 pages. Available in PDF, EPUB and Kindle. Book excerpt: There have been remarkable advances towards discovering agents that exhibit selectivity and sequence-specificity for DNA, as well as understanding the interactions that underlie its propensity to bind molecules. This progress has important applications in many areas of biotechnology and medicine, notably in cancer treatment as well as in future gene targeting therapies. The editor and contributing authors are leaders in their fields and provide useful perspectives from diverse and interdisciplinary backgrounds on the current status of this broad area. The role played by chemistry is a unifying theme. Early chapters cover methodologies to evaluate DNA-interactive agents and then the book provides examples of DNA-interactive molecules and technologies in development as therapeutic agents. DNA-binding metal complexes, peptide and polyamide–DNA interactions, and gene targeting tools are some of the most compelling topics treated in depth. This book will be a valuable resource for postgraduate students and researchers in chemical biology, biochemistry, structural biology and medicinal fields. It will also be of interest to supramolecular chemists and biophysicists.
Download or read book Synthesis of Small Molecules Targeting RNA written by Qi Liu and published by . This book was released on 2004 with total page 370 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 Manfred Egender written by Manfred Egender and published by . This book was released on 1992 with total page 14 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Therapeutic Oligonucleotides written by Jens Kurreck and published by Royal Society of Chemistry. This book was released on 2008 with total page 362 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a compelling overall update on current status of RNA interference
Download or read book Principles of Nucleic Acid Structure written by Stephen Neidle and published by Elsevier. This book was released on 2010-07-26 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt: This unique and practical resource provides the most complete and concise summary of underlying principles and approaches to studying nucleic acid structure, including discussion of x-ray crystallography, NMR, molecular modelling, and databases. Its focus is on a survey of structures especially important for biomedical research and pharmacological applications. To aid novices, Principles of Nucleic Acid Structure includes an introduction to technical lingo used to describe nucleic acid structure and conformations (roll, slide, twist, buckle, etc.). This completely updated edition features expanded coverage of the latest advances relevant to recognition of DNA and RNA by small molecules and proteins. In particular, the reader will find extensive new discussions on: RNA folding, ribosome structure and antibiotic interactions, DNA quadruplexes, DNA and RNA protein complexes, and short interfering RNA (siRNA). This handy guide ends with a complete list of resources, including relevant online databases and software. Completely updated with expanded discussion of topics such as RNA folding, ribosome structure and antibiotic interactions, DNA quadruplexes, DNA and RNA protein complexes, and short interfering RNA (siRNA) Includes a complete list of resources, including relevant online databases and software Defines technical lingo for novices
Download or read book Development of Nucleic Acid Targeting Molecules written by Fai Alkathiri and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular docking is a widely used and effective structure-based computational strategy for predicting dynamics between ligands and receptors. Until now the docking software were developed for the protein-ligand interactions and very few docking tools were developed exclusively for the docking of small molecules on the nucleic acid structures like the DNA and RNA. The progress in algorithms and the need for deeper understanding of ligand-nucleic acid interactions more focused, and specialized tools are being developed to explore this hindered area of drug discovery. This chapter is focused on and discus in details about various tools available for docking with nucleic acids and how the rejuvenation of machine learning methods is making its impact on the development of these docking programs.
Download or read book Molecular Targeting of Nucleic Acid Secondary Structures written by Mikkel Stockendahl Christensen and published by . This book was released on 2007 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Small Molecule Transcription Factor Inhibitors in Oncology written by Khondaker Miraz Rahman and published by Royal Society of Chemistry. This book was released on 2018-09-06 with total page 214 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book highlights recent progress in the development of small-molecule inhibitors of oncogenic transcription factors and is relevant for postgraduates, researchers and practitioners.
Download or read book Targeting RNA with Small Molecules written by Emily Satkiewicz and published by . This book was released on 2011 with total page 217 pages. Available in PDF, EPUB and Kindle. Book excerpt: The high functionality and complex three dimensional structure of RNA offers promise for the development of a wide range of RNA-targeting therapeutics. Previous studies of known RNA-friendly molecules reveal properties which promote RNA-small molecule interactions, such as distinct edges containing multiple hydrogen-bonding donors and acceptors, positively charged amino groups, opportunities for pi-stacking, and molecule rigidity. TAN 1057 is a natural dipeptide antibiotic thought to inhibit translation through interactions with ribosomal RNA. Modeling studies of the dihydropyrimidinone core of TAN 1057 show multiple potential interactions with each of the RNA bases. The synthesis of potential "RNA-friendly" small molecules was carried out using derivatives of the natural core of TAN 1057. Coupling of these derivative cores with various side groups containing "RNA-friendly" properties sought to promote further RNA-small molecule interactions. Three cores in addition to the natural core were synthesized and derivatized when possible, creating a small library of compounds to be tested against functional regions of RNA. Specifically, this work sought to target functional RNA within the hepatitis C virus and thymidylate synthase RNA, and structure activity relationships were explored.
