Topologically Constrained Dna Intercalators

Topologically Constrained Dna Intercalators PDF Author: Carol R. Lamberson
Publisher:
ISBN:
Category :
Languages : en
Pages : 308

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Book Description
The synthesis and DNA binding properties of three macrocyclic diacridines (31, 32 and 33) is discussed. The two acridines are connected by linker chains at the 4- and 9-positions. Macrocycles 31 and 32 are linked via spermine at the 9-position and have been shown to bind to DNA by bisintercalation using absorption spectroscopy titrations, thermal denaturation studies, and viscometric titrations of both calf thymus DNA and closed circular supercoiled DNA. Macrocycle 31 dissociates 10 to 40 times slower from poly(d(A-T)) $sb2$ and poly(d(G-C)) $sb2$ than its analogous mono-linked analogue, spermine diacridine (7). $sp1$H NMR studies of 31 complexed to d(CGCG)$sb2$ indicate that the macrocycle binds to DNA by formation of a catenated complex in which one linking chain is located in opposite grooves of the DNA. The NMR studies and absorption spectral titrations suggest that 31 binds by insertion of the acridines on each side of one base pair in violation of the neighbor exclusion principle. Macrocycle 33 has a diamide linker chain at the 9-position of the acridine rings. This molecule binds to DNA by intercalation as evident from its ability to remove and reverse the supercoils in closed circular DNA. However, the results are inconclusive as to whether it binds by mono- or bisintercalation. The mono-linked diacridine 34 has been shown to bind to DNA by bisintercalation. The preliminary synthetic results for a novel trisintercalator are discussed. Trimer 35 consists of a naphthalene diimide as the central chromophore and two 9-aminoacridines as the terminal chromophores. Trimer 35 was synthesized from 1,4,5,8-naphthalene dianhydride which was reacted with the mono-Boc protected diamine to give the N,N$spprime$-disubstituted naphthalene diimide. After deprotection, the diimide was reacted with two moles of 9-phenoxyacridine to produce 35. The dimer 36 containing a naphthalene diimide and one 9-aminoacridine was synthesized in a similar manner.

Topologically Constrained Dna Intercalators

Topologically Constrained Dna Intercalators PDF Author: Carol R. Lamberson
Publisher:
ISBN:
Category :
Languages : en
Pages : 308

Get Book Here

Book Description
The synthesis and DNA binding properties of three macrocyclic diacridines (31, 32 and 33) is discussed. The two acridines are connected by linker chains at the 4- and 9-positions. Macrocycles 31 and 32 are linked via spermine at the 9-position and have been shown to bind to DNA by bisintercalation using absorption spectroscopy titrations, thermal denaturation studies, and viscometric titrations of both calf thymus DNA and closed circular supercoiled DNA. Macrocycle 31 dissociates 10 to 40 times slower from poly(d(A-T)) $sb2$ and poly(d(G-C)) $sb2$ than its analogous mono-linked analogue, spermine diacridine (7). $sp1$H NMR studies of 31 complexed to d(CGCG)$sb2$ indicate that the macrocycle binds to DNA by formation of a catenated complex in which one linking chain is located in opposite grooves of the DNA. The NMR studies and absorption spectral titrations suggest that 31 binds by insertion of the acridines on each side of one base pair in violation of the neighbor exclusion principle. Macrocycle 33 has a diamide linker chain at the 9-position of the acridine rings. This molecule binds to DNA by intercalation as evident from its ability to remove and reverse the supercoils in closed circular DNA. However, the results are inconclusive as to whether it binds by mono- or bisintercalation. The mono-linked diacridine 34 has been shown to bind to DNA by bisintercalation. The preliminary synthetic results for a novel trisintercalator are discussed. Trimer 35 consists of a naphthalene diimide as the central chromophore and two 9-aminoacridines as the terminal chromophores. Trimer 35 was synthesized from 1,4,5,8-naphthalene dianhydride which was reacted with the mono-Boc protected diamine to give the N,N$spprime$-disubstituted naphthalene diimide. After deprotection, the diimide was reacted with two moles of 9-phenoxyacridine to produce 35. The dimer 36 containing a naphthalene diimide and one 9-aminoacridine was synthesized in a similar manner.

Statistical Mechanics of Topologically Constrained DNA and Nucleoprotein Complexes

Statistical Mechanics of Topologically Constrained DNA and Nucleoprotein Complexes PDF Author: Stefan Michael Giovan
Publisher:
ISBN:
Category : DNA repair
Languages : en
Pages : 212

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Book Description
A complex connection exists between the 3 dimensional topological state of DNA in living organisms and biological processes including gene expression, DNA replication, recombination and repair. A significant limitation in developing a detailed, quantitative understanding of this connection is due to a lack of rigorous methods to calculate statistical mechanical properties of DNA molecules with complex topologies, including supercoiling, looping and knotting. This dissertation's main focus is on developing such methods and applying them to realistic DNA and nucleoprotein models. In chapter 2, a method is presented to calculate free energies and J factors of protein mediated DNA loops by normal mode analysis (NMA). This method is similar to calculations performed previously but with several significant advances. We apply the method to the specific case of DNA looping mediated by Cre recombinase protein. J factors calculated by our method are compared to experimental measurements to extract geometric and elastic properties of the Cre-DNA synaptic complex. In particular, the results suggest the existence of a synaptic complex that is more flexible than previously expected and may be explained by a stable intermediate in the reaction pathway that deviates significantly from the planar crystal structure. Calculating free energies of DNA looping is difficult in general, especially when considering intermediate length scales such as plasmid sized DNA which may readily adopt multiple topological states. In chapter 3, a novel method is presented to obtain free energies of semiflexible biopolymers with fixed topologies and arbitrary ratios of contour length L to persistence length P. High accuracy is demonstrated by calculating free energies of specific DNA knots with L/P = 20 and L/P = 40, corresponding to DNA lengths of 3000 and 6000 base pairs, respectively. We then apply the method to study the free-energy landscape for a model of a synaptic nucleoprotein complex containing a pair of looped domains, revealing a bifurcation in the location of optimal synapse (crossover) sites. This transition is relevant to target-site selection by DNA-binding proteins that occupy multiple DNA sites separated by large linear distances along the genome, a problem that arises naturally in gene regulation, DNA recombination, and the action of type-II topoisomerases.

Topology and Physics of Circular DNA (1992)

Topology and Physics of Circular DNA (1992) PDF Author: Alexander Vologodskii
Publisher: CRC Press
ISBN: 135135583X
Category : Medical
Languages : en
Pages : 192

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Book Description
Topology and Physics of Circular DNA presents comprehensive coverage of the physical properties of circular DNA. The author examines how topological constraints arising from cyclization of DNA lead to distinctive properties that make closed molecules radically different from linear DNA. The phenomenon of supercoiling, its geometric and topological analysis, and the formation of noncanonical structures in circular DNA under the influence of supercoiling are emphasized. The combination of consistent theoretical analysis and detailed treatment of major experimental approaches make Topology and Physics of Circular DNA an important reference volume for biophysicists, biochemists, molecular biologists, and researchers and students who want to expand their understanding of circular DNA.

Naphthalenediimide and its Congeners

Naphthalenediimide and its Congeners PDF Author: G Dan Pantos
Publisher: Royal Society of Chemistry
ISBN: 1788011198
Category : Science
Languages : en
Pages : 359

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Book Description
The past decade has seen significant advances in naphthalenediimide and rylene diimide chemistry. This book discusses the recent advances in this field, and highlights potential and real applications for the molecules. Such applications include organic photovoltaics, anion-slides, DNA binders, and building blocks for complex molecular topologies. Naphthalenediimide and its Congeners is the first book in this rapidly developing area, and will be essential reference material for postdoctoral researchers and postgraduate students. This text will also provide a solid foundation for further development of naphthalenediimide chemistry. Written by leaders in the field, the book includes chapters on the supramolecular chemistry of naphthalenediimide; DNA intercalators; ion transport through membranes; naphthalenediimide based photovoltaics; and rylene dyes, amongst others. Naphthalenediimide and its Congeners is a detailed and in depth resource relevant not only to supramolecular and materials chemists, but also to the larger chemistry and materials science fields.

Chromosomal Aberrations

Chromosomal Aberrations PDF Author: Günter Obe
Publisher: Springer Science & Business Media
ISBN: 3642756824
Category : Science
Languages : en
Pages : 328

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Book Description
Chromosomale Mutationen sind eine der m|glichen Ursachen f}r Ver{nderungen der Erbinformation. Neben grunds{tzlichen As- pekten, wie Reparaturmechanismen der Zelle oder Ursachen von Chromosomenver{nderungen, werden angewandte Aspekte, z.B. Chromosomen als Testindikatoren der Toxizit{t, behandelt.

Small Molecule DNA and RNA Binders

Small Molecule DNA and RNA Binders PDF Author: Martine Demeunynck
Publisher: John Wiley & Sons
ISBN: 3527605665
Category : Science
Languages : en
Pages : 754

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Book Description
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.

The Chemical Biology of Nucleic Acids

The Chemical Biology of Nucleic Acids PDF Author: Günter Mayer
Publisher: John Wiley & Sons
ISBN: 1119957265
Category : Science
Languages : en
Pages : 595

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Book Description
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.

Encyclopedia of Analytical Science

Encyclopedia of Analytical Science PDF Author:
Publisher: Elsevier
ISBN: 008101984X
Category : Science
Languages : en
Pages : 5142

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Book Description
The third edition of the Encyclopedia of Analytical Science, Ten Volume Set is a definitive collection of articles covering the latest technologies in application areas such as medicine, environmental science, food science and geology. Meticulously organized, clearly written and fully interdisciplinary, the Encyclopedia of Analytical Science, Ten Volume Set provides foundational knowledge across the scope of modern analytical chemistry, linking fundamental topics with the latest methodologies. Articles will cover three broad areas: analytical techniques (e.g., mass spectrometry, liquid chromatography, atomic spectrometry); areas of application (e.g., forensic, environmental and clinical); and analytes (e.g., arsenic, nucleic acids and polycyclic aromatic hydrocarbons), providing a one-stop resource for analytical scientists. Offers readers a one-stop resource with access to information across the entire scope of modern analytical science Presents articles split into three broad areas: analytical techniques, areas of application and and analytes, creating an ideal resource for students, researchers and professionals Provides concise and accessible information that is ideal for non-specialists and readers from undergraduate levels and higher

Mitochondrial DNA

Mitochondrial DNA PDF Author: Thomas J. Nicholls
Publisher: Springer Nature
ISBN: 1071629220
Category : Science
Languages : en
Pages : 465

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Book Description
This volume compiles a comprehensive range of methods to study key aspects of mitochondrial DNA including nucleoid structure and packaging, replication, genome integrity, and disease. Chapters are organized into eight methodological sections that cover in vitro and in vivo methods, including for mtDNA isolation, visualization, deep sequencing, gene editing, and diagnostic aspects of mtDNA disease. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and methods, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, Mitochondrial DNA: Methods and Protocols aims to be useful and informative for researchers and clinicians with an interest in mitochondrial DNA.

Issues in Biochemistry and Geochemistry: 2011 Edition

Issues in Biochemistry and Geochemistry: 2011 Edition PDF Author:
Publisher: ScholarlyEditions
ISBN: 1464963894
Category : Science
Languages : en
Pages : 2344

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Book Description
Issues in Biochemistry and Geochemistry / 2011 Edition is a ScholarlyEditions™ eBook that delivers timely, authoritative, and comprehensive information about Biochemistry and Geochemistry. The editors have built Issues in Biochemistry and Geochemistry: 2011 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Biochemistry and Geochemistry in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Issues in Biochemistry and Geochemistry / 2011 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.