Potential Anticancer Activity Via Inhibition of Telomerase Binding: Investigation of Stabilization Factors for G-Quadruplex Structures

Potential Anticancer Activity Via Inhibition of Telomerase Binding: Investigation of Stabilization Factors for G-Quadruplex Structures PDF Author: Tamaki Chiba
Publisher:
ISBN:
Category : DNA.
Languages : en
Pages : 0

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Book Description
Telomerase activity is expressed in approximately 85 % of human cancer cells. The overexpression of telomerase in cancer cells is sufficient enough to maintain the length of telomeres and overcome cellular senescence or apoptosis, which explains the immortal feature of cancer cells. In order to cease the immortality of cancer cells caused by telomerase, a strategy that focuses on the inhibition of telomerase activity has been developed. Due to the feature of G-rich human telomeric sequence (T2AG3 repeats), the telomeres can form a G-quadruplex secondary structure whose steric hindrance may disrupt the telomerase binding. In this project, in order to prevent telomerase from accessing and elongating the telomeres, we investigated the factors that stabilize G-quadruplex structures by using UV-Vis Spectroscopy, Fluorescence Spectroscopy and Surface Plasmon Resonance (SPR). We showed that, among the monovalent cations, potassium maximized the stabilization. The stabilization of DNA G-quadruplex was further enhanced in the presence of ligands such as TmPyP4 and its manganese derivative, Mn(Ⅲ)TmPyP4. We also compared the stability of DNA quadruplex and RNA quadruplex. Interestingly, RNA quadruplex showed greater thermodynamic stability than DNA quadruplex under the same experimental conditions. However, RNA quadruplex was not stabilized by the porphyrin ligands we used. Although the conformation analysis of G-quadruplex and the modeling of G-quadruplex ligands are still under investigation, this project gives an insight into improving the stability of both DNA and RNA quadruplex structures.

Potential Anticancer Activity Via Inhibition of Telomerase Binding: Investigation of Stabilization Factors for G-Quadruplex Structures

Potential Anticancer Activity Via Inhibition of Telomerase Binding: Investigation of Stabilization Factors for G-Quadruplex Structures PDF Author: Tamaki Chiba
Publisher:
ISBN:
Category : DNA.
Languages : en
Pages : 0

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Book Description
Telomerase activity is expressed in approximately 85 % of human cancer cells. The overexpression of telomerase in cancer cells is sufficient enough to maintain the length of telomeres and overcome cellular senescence or apoptosis, which explains the immortal feature of cancer cells. In order to cease the immortality of cancer cells caused by telomerase, a strategy that focuses on the inhibition of telomerase activity has been developed. Due to the feature of G-rich human telomeric sequence (T2AG3 repeats), the telomeres can form a G-quadruplex secondary structure whose steric hindrance may disrupt the telomerase binding. In this project, in order to prevent telomerase from accessing and elongating the telomeres, we investigated the factors that stabilize G-quadruplex structures by using UV-Vis Spectroscopy, Fluorescence Spectroscopy and Surface Plasmon Resonance (SPR). We showed that, among the monovalent cations, potassium maximized the stabilization. The stabilization of DNA G-quadruplex was further enhanced in the presence of ligands such as TmPyP4 and its manganese derivative, Mn(Ⅲ)TmPyP4. We also compared the stability of DNA quadruplex and RNA quadruplex. Interestingly, RNA quadruplex showed greater thermodynamic stability than DNA quadruplex under the same experimental conditions. However, RNA quadruplex was not stabilized by the porphyrin ligands we used. Although the conformation analysis of G-quadruplex and the modeling of G-quadruplex ligands are still under investigation, this project gives an insight into improving the stability of both DNA and RNA quadruplex structures.

Protein-Nucleic Acid Interactions

Protein-Nucleic Acid Interactions PDF Author: Phoebe A. Rice
Publisher: Royal Society of Chemistry
ISBN: 0854042725
Category : Science
Languages : en
Pages : 417

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Book Description
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.

Telomeres and Telomerase in Cancer

Telomeres and Telomerase in Cancer PDF Author: Keiko Hiyama
Publisher: Springer Science & Business Media
ISBN: 1603278796
Category : Medical
Languages : en
Pages : 380

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Book Description
Telomerase, an enzyme that maintains telomeres and endows eukaryotic cells with immortality, was first discovered in tetrahymena in 1985. In 1990s, it was proven that this enzyme also plays a key role in the infinite proliferation of human cancer cells. Now telomere and telomerase are widely accepted as important factors involved in cancer biology, and as promising diagnostic tools and therapeutic targets. Recently, role of telomerase in “cancer stem cells” has become another attractive story. Until now, there are several good books on telomere and telomerase focusing on biology in ciliates, yeasts, and mouse or basic sciences in human, providing basic scientists or students with updated knowledge.

Stabilization of G-quadruplex Structures by Organometallic Complexes

Stabilization of G-quadruplex Structures by Organometallic Complexes PDF Author: Hang Thanh Hoang
Publisher:
ISBN:
Category : Analytical chemistry
Languages : en
Pages : 0

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Book Description
Telomere shortening is primarily involved in cell death and cellular aging. However, telomerase can reverse the shortening process and allow cells to overcome apoptosis. Telomerase activity is expressed in 85-90% of cancer cells. Binding of this enzyme can be prevented by the formation of G-quadruplex structures, which include stacks of G-tetrads formed by telomeric TTAGGG tandem repeats. Therefore, G-quadruplex stability is crucial to the inhibition of telomerase activity and ligand-induced quadruplex stabilization emerges as a potential chemotherapeutic pathway due to its high selectivity and specificity towards cancer cells. Our project aims to understand the stabilization mechanism of DNA/RNA G-quadruplex by organometallic compounds using UV/Vis spectroscopy and Isothermal Titration Calorimetry (ITC). We have shown that quadruplex stability is increased by potassium ions and further enhanced by the cationic porphyrin ligands TMPyP4 and Mn(III) TMPyP4. We also found that the anionic copper (II) phthalocyanine Cu-APC complex, discovered by the Sugimoto group, potentially interacts with both DNA and RNA quadruplexes. The nonionic benzothiophene platinum(II) complex L3, synthesized by the Anderson lab, also interacts with DNA G- quadruplex and potentially stabilizes the structures. Our studies have provided insights into improving quadruplex stability by organometallic ligands and how their stabilizing effects differ due to structural differences.

Quadruplex Nucleic Acids

Quadruplex Nucleic Acids PDF Author: Stephen Neidle
Publisher: Royal Society of Chemistry
ISBN: 1847555292
Category : Science
Languages : en
Pages : 301

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Book Description
Guanine rich DNA has been known for decades to form unusual structures, although their biological relevance was little understood. Recent advances have demonstrated that quadruplex structures can play a role in gene expression and provide opportunities for a new class of anticancer therapeutics. A number of quadruplex-specific proteins have also been discovered. Quadruplex Nucleic Acids discusses all aspects of the fundamentals of quadruplex structures, including their structure in solution and the crystalline state, the kinetics of quadruplex folding, and the role of cations in structure and stability. The biology of quadruplexes and G-rich genomic regions and G-quartets in supramolecular chemistry and nanoscience are also considered. Surveying the current state of knowledge, and with contributions from leading experts, this is the first comprehensive review of this rapidly growing area. Quadruplex Nucleic Acids is ideal for researchers interested in areas related to chemistry, chemical biology, medicinal chemistry, molecular pharmacology, and structural and molecular biology.

Medicinal Chemistry of Nucleic Acids

Medicinal Chemistry of Nucleic Acids PDF Author: Li-He Zhang
Publisher: John Wiley & Sons
ISBN: 0470596686
Category : Medical
Languages : en
Pages : 477

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Book Description
Complete, up-to-date coverage of the broad area of nucleic acid chemistry and biology Assembling contributions from a collection of authors with expertise in all areas of nucleic acids, medicinal chemistry, and therapeutic applications, Medicinal Chemistry of Nucleic Acids presents a thorough overview of nucleic acid chemistry—a rapidly evolving and highly challenging discipline directly responsible for the development of antiviral and antitumor drugs. This reliable resource delves into a multitude of subject areas involving the study of nucleic acids—such as the new advances in genome sequencing, and the processes for creating RNA interference (RNAi) based drugs—to assist pharmaceutical researchers in removing roadblocks that hinder their ability to predict drug efficacy. Offering the latest cutting-edge science in this growing field, Medicinal Chemistry of Nucleic Acids includes: In-depth coverage of the development and application of modified nucleosides and nucleotides in medicinal chemistry A close look at a large range of current topics on nucleic acid chemistry and biology Essential information on the use of nucleic acid drugs to treat diseases like cancer A thorough exploration of siRNA for RNAi and the regulation of microRNA, non-coding RNA (ncRNA), a newly developing and exciting research area Thorough in its approach and promising in its message, Medicinal Chemistry of Nucleic Acids probes the new domains of pharmaceutical research—and exposes readers to a wealth of new drug discovery opportunities emerging in the dynamic field of nucleic acid chemistry.

Ferroptosis in cancer and beyond

Ferroptosis in cancer and beyond PDF Author: Yanqing Liu
Publisher: Frontiers Media SA
ISBN: 2832513425
Category : Science
Languages : en
Pages : 452

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G-Quadruplex Nucleic Acids

G-Quadruplex Nucleic Acids PDF Author: Danzhou Yang
Publisher: Humana
ISBN: 9781493996681
Category : Medical
Languages : en
Pages : 437

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Book Description
This volume covers the structures, properties, and functions of G-quadruplexes in a wide range of biological disciplines, including therapeutic intervention and biomaterial application. The chapters in this book explore a wide range of vital and new experimental techniques used in the study of G-quadruplexes. 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 tips on troubleshooting and avoiding known pitfalls. Practical and cutting-edge, G-Quadruplex DNA: Methods and Protocols is a valuable resource for both novice and experienced researchers who work in biophysics, structural biology, computational biology, biochemistry, and molecular and cell biology, and who want to learn more about the potential roles and effects of G-quadruplex in these fields.

Neuroblastoma

Neuroblastoma PDF Author: Chandrika Gowda
Publisher: BoD – Books on Demand
ISBN: 953513583X
Category : Medical
Languages : en
Pages : 169

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Book Description
Neuroblastoma (NBL) is the most common extracranial solid tumor of childhood, with about 700 new cases of neuroblastoma seen each year in the United States. The 5-year survival rate for children with high-risk NBL is only 50-60%, and this survival rate has not improved over the last 10 years. High-risk patients receive multimodality treatment, including chemotherapy, surgery, radiation therapy, biologic therapy and immunotherapy, all of which are associated with significant morbidity. Recent years have seen many advances in treatment of neuroblastoma, including therapeutic MIBG, immunotherapy, and personalized targeted therapy based on the genetic alterations seen in the tumor. The primary objective of this book is to provide the readers with a comprehensive review of neuroblastoma, from clinical aspects and the currently available treatment to recent advancements and future directions in the field of NBL treatment. The topics and chapters have been compiled keeping in mind a diverse group of readers in different areas of specialty such as pediatric oncology, surgery, radiation oncology, and immunology, as well as physician scientists and basic researchers working in the field of neuroblastoma.

Cumulated Index Medicus

Cumulated Index Medicus PDF Author:
Publisher:
ISBN:
Category : Medicine
Languages : en
Pages : 1828

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Book Description