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Shape-dependent Molecular Recognition of Specific Sequences of DNA by Heterocyclic Cations

Shape-dependent Molecular Recognition of Specific Sequences of DNA by Heterocyclic Cations PDF Author:
Publisher:
ISBN:
Category : Cations
Languages : en
Pages :

Book Description
DB921 and DB911 are biphenyl-benzimidazole-diamidine isomers with a central para- and meta-substituted phenyl group, respectively. Unexpectedly, linear DB921 has much stronger binding affinity with DNA than its curved isomer, DB911. This is quite surprising and intriguing since DB911 has the classical curved shape generally required for strong minor groove binding while DB921 clearly does not match the groove shape. Several biophysical techniques including thermal melting (Tm), circular dichroism (CD), biosensor-surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) have been utilized to investigate the interactions between these compounds and DNA. The structure of the DB921-DNA complex reveals that DB921 binds to DNA with a reduced twist of the biphenyl for better fit of DB921 into the minor groove. A bound water molecule complements the curvature of DB921 and contributes for tight binding by forming H-bonds with both DNA and DB921. Structure-affinity relationship studies of a series of DB921 analogs show that the benzimidazole group is one of the key groups of DB921 for its strong binding to the minor groove. Thermodynamic studies show that the stronger binding of DB921 is due to a more favorable binding enthalpy compared to DB911 even though the complex formation with DNA for these compounds are all predominantly entropically driven. DB921 also has more negative heat capacity change than DB911. The initial studies of inhibition of the interaction between an AT hook peptide of HMGA proteins and its target DNA by a set of diamidine AT-minor groove binders using biosensor-SPR technique show that the inhibitory ranking order is consistent with that of binding affinity and linear-shaped DB921 still has excellent inhibitory effects. These heterocyclic cations rapidly inhibit the binding of DBD2 peptide to the DNA and may only block the specific AT binding of the peptide without hindering the non-specific binding interaction. The results of this project have shown that DB921 represents a new novel effective minor groove binder that does not fit the traditional model and is a potential inhibitor for DNA/protein complexes.

Shape-dependent Molecular Recognition of Specific Sequences of DNA by Heterocyclic Cations

Shape-dependent Molecular Recognition of Specific Sequences of DNA by Heterocyclic Cations PDF Author:
Publisher:
ISBN:
Category : Cations
Languages : en
Pages :

Book Description
DB921 and DB911 are biphenyl-benzimidazole-diamidine isomers with a central para- and meta-substituted phenyl group, respectively. Unexpectedly, linear DB921 has much stronger binding affinity with DNA than its curved isomer, DB911. This is quite surprising and intriguing since DB911 has the classical curved shape generally required for strong minor groove binding while DB921 clearly does not match the groove shape. Several biophysical techniques including thermal melting (Tm), circular dichroism (CD), biosensor-surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) have been utilized to investigate the interactions between these compounds and DNA. The structure of the DB921-DNA complex reveals that DB921 binds to DNA with a reduced twist of the biphenyl for better fit of DB921 into the minor groove. A bound water molecule complements the curvature of DB921 and contributes for tight binding by forming H-bonds with both DNA and DB921. Structure-affinity relationship studies of a series of DB921 analogs show that the benzimidazole group is one of the key groups of DB921 for its strong binding to the minor groove. Thermodynamic studies show that the stronger binding of DB921 is due to a more favorable binding enthalpy compared to DB911 even though the complex formation with DNA for these compounds are all predominantly entropically driven. DB921 also has more negative heat capacity change than DB911. The initial studies of inhibition of the interaction between an AT hook peptide of HMGA proteins and its target DNA by a set of diamidine AT-minor groove binders using biosensor-SPR technique show that the inhibitory ranking order is consistent with that of binding affinity and linear-shaped DB921 still has excellent inhibitory effects. These heterocyclic cations rapidly inhibit the binding of DBD2 peptide to the DNA and may only block the specific AT binding of the peptide without hindering the non-specific binding interaction. The results of this project have shown that DB921 represents a new novel effective minor groove binder that does not fit the traditional model and is a potential inhibitor for DNA/protein complexes.

Dissertation Abstracts International

Dissertation Abstracts International PDF Author:
Publisher:
ISBN:
Category : Dissertations, Academic
Languages : en
Pages : 846

Book Description


Handbook of Chemical Biology of Nucleic Acids

Handbook of Chemical Biology of Nucleic Acids PDF Author: Naoki Sugimoto
Publisher: Springer Nature
ISBN: 9811997764
Category : Science
Languages : en
Pages : 2847

Book Description
This handbook is the first to comprehensively cover nucleic acids from fundamentals to recent advances and applications. It is divided into 10 sections where authors present not only basic knowledge but also recent research. Each section consists of extensive review chapters covering the chemistry, biology, and biophysics of nucleic acids as well as their applications in molecular medicine, biotechnology and nanotechnology. All sections within this book are: Physical Chemistry of Nucleic Acids (Section Editor: Prof. Roland Winter), Structural Chemistry of Nucleic Acids (Section Editor: Prof. Janez Plavec), Organic Chemistry of Nucleic Acids (Section Editor: Prof. Piet Herdewijin), Ligand Chemistry of Nucleic Acids (Section Editor: Prof. Marie-Paule Teulade-Fichou), Nucleic Acids and Gene Expression (Section Editor: Prof. Cynthia Burrows), Analytical Methods and Applications of Nucleic Acids (Section Editor: Prof. Chaoyong Yang), Nanotechnology and Nanomaterial Biology of Nucleic Acids (Section Editor: Prof. Zhen Xi), Nucleic Acids Therapeutics (Section Editor: Prof. Katherine Seley-Radtke), Biotechnology and Synthetic Biology of Nucleic Acids (Section Editor: Prof. Eriks Rozners), Functional Nucleic Acids (Section Editor: Prof. Keith R. Fox). The handbook is edited by outstanding leaders with contributions written by international renowned experts. It is a valuable resource not only for researchers but also graduate students working in areas related to nucleic acids who would like to learn more about their important role and potential applications.

Theory of Solutions

Theory of Solutions PDF Author: John G. Kirkwood
Publisher: CRC Press
ISBN: 9780677010304
Category : Science
Languages : en
Pages : 320

Book Description


DNA

DNA PDF Author: James D. Watson
Publisher: Knopf
ISBN: 0307521486
Category : Science
Languages : en
Pages : 464

Book Description
Fifty years ago, James D. Watson, then just twentyfour, helped launch the greatest ongoing scientific quest of our time. Now, with unique authority and sweeping vision, he gives us the first full account of the genetic revolution—from Mendel’s garden to the double helix to the sequencing of the human genome and beyond. Watson’s lively, panoramic narrative begins with the fanciful speculations of the ancients as to why “like begets like” before skipping ahead to 1866, when an Austrian monk named Gregor Mendel first deduced the basic laws of inheritance. But genetics as we recognize it today—with its capacity, both thrilling and sobering, to manipulate the very essence of living things—came into being only with the rise of molecular investigations culminating in the breakthrough discovery of the structure of DNA, for which Watson shared a Nobel prize in 1962. In the DNA molecule’s graceful curves was the key to a whole new science. Having shown that the secret of life is chemical, modern genetics has set mankind off on a journey unimaginable just a few decades ago. Watson provides the general reader with clear explanations of molecular processes and emerging technologies. He shows us how DNA continues to alter our understanding of human origins, and of our identities as groups and as individuals. And with the insight of one who has remained close to every advance in research since the double helix, he reveals how genetics has unleashed a wealth of possibilities to alter the human condition—from genetically modified foods to genetically modified babies—and transformed itself from a domain of pure research into one of big business as well. It is a sometimes topsy-turvy world full of great minds and great egos, driven by ambitions to improve the human condition as well as to improve investment portfolios, a world vividly captured in these pages. Facing a future of choices and social and ethical implications of which we dare not remain uninformed, we could have no better guide than James Watson, who leads us with the same bravura storytelling that made The Double Helix one of the most successful books on science ever published. Infused with a scientist’s awe at nature’s marvels and a humanist’s profound sympathies, DNA is destined to become the classic telling of the defining scientific saga of our age.

Encyclopedia of Analytical Science

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

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

How Tobacco Smoke Causes Disease

How Tobacco Smoke Causes Disease PDF Author: United States. Public Health Service. Office of the Surgeon General
Publisher:
ISBN:
Category : Government publications
Languages : en
Pages : 728

Book Description
This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.

Carbohydrate Recognition

Carbohydrate Recognition PDF Author: Binghe Wang
Publisher: John Wiley & Sons
ISBN: 0470592079
Category : Medical
Languages : en
Pages : 448

Book Description
This book contains contributions from interdisciplinary scientists to collectively address the issue of targeting carbohydrate recognition for the development of novel therapeutic and diagnostic agents. The book covers (1) biological problems involving carbohydrate recognition, (2) structural factors mediating carbohydrate recognition, (3) design and synthesis of lectin mimics that recognize carbohydrate ligands with high specificity and affinity, and (4) modulation of biological and pathological processes through carbohydrate recognition.

Principles of Nucleic Acid Structure

Principles of Nucleic Acid Structure PDF Author: Wolfram Saenger
Publisher: Springer Science & Business Media
ISBN: 1461251907
Category : Science
Languages : en
Pages : 574

Book Description
New textbooks at all levels of chemistry appear with great regularity. Some fields like basic biochemistry, organic reaction mechanisms, and chemical ther modynamics are well represented by many excellent texts, and new or revised editions are published sufficiently often to keep up with progress in research. However, some areas of chemistry, especially many of those taught at the grad uate level, suffer from a real lack of up-to-date textbooks. The most serious needs occur in fields that are rapidly changing. Textbooks in these subjects usually have to be written by scientists actually involved in the research which is advancing the field. It is not often easy to persuade such individuals to set time aside to help spread the knowledge they have accumulated. Our goal, in this series, is to pinpoint areas of chemistry where recent progress has outpaced what is covered in any available textbooks, and then seek out and persuade experts in these fields to produce relatively concise but instructive introductions to their fields. These should serve the needs of one semester or one quarter graduate courses in chemistry and biochemistry. In some cases the availability of texts in active research areas should help stimulate the creation of new courses. CHARLES R. CANTOR New York Preface This monograph is based on a review on polynucleotide structures written for a book series in 1976.

Natural Product Biosynthesis

Natural Product Biosynthesis PDF Author: Christopher T. Walsh
Publisher: Royal Society of Chemistry
ISBN: 1788010760
Category : Science
Languages : en
Pages : 787

Book Description
This textbook describes the types of natural products, the biosynthetic pathways that enable the production of these molecules, and an update on the discovery of novel products in the post-genomic era.