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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.
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.
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.
Author: Paul Edrick Schutt
Publisher:
ISBN:
Category :
Languages : en
Pages : 74
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Book Description
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.
Author: Lucy Andrews
Publisher: Springer Science & Business Media
ISBN: 1588296830
Category : Medical
Languages : en
Pages : 197
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Book Description
This volume presents a compendium of the most recent and advanced methods applied to the rapidly expanding field of telomerase inhibition. The techniques described provide the researcher with a diverse and comprehensive set of tools for the study of telomerase inhibition. The volume is aimed at biochemists, molecular biologists, cancer researchers, and geneticists.
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.
Author:
Publisher: Academic Press
ISBN: 0128210184
Category : Science
Languages : en
Pages : 564
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Book Description
The realisation that human, animal, viral and bacterial genomes all contain over-representation of higher-order quadruplex structures in regulatory and other pharmacologically-useful regions, has led to a large number of studies aimed at exploiting this findings for therapeutic and diagnostic purposes. Quadruplex-binding small molecules are starting to be evaluated in human clinical trials. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Annual Reports in Medicinal Chemistry series
Author: Heinz-Peter Nasheuer
Publisher: Springer Science & Business Media
ISBN: 9048134714
Category : Medical
Languages : en
Pages : 346
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Book Description
Since the establishment of the DNA structure researchers have been highly interested in the molecular basis of the inheritance of genes and of genetic disorders. Scientific investigations of the last two decades have shown that, in addition to oncogenic viruses and signalling pathways alterations, genomic instability is important in the development of cancer. This view is supported by the findings that aneuploidy, which results from chromosome instability, is one of the hallmarks of cancer cells. Chromosomal instability also underpins our fundamental principles of understanding tumourigenesis: It thought that cancer arises from the sequential acquisition of genetic alterations in specific genes. In this hypothesis, these rare genetic events represent rate-limiting ‘bottlenecks’ in the clonal evolution of a cancer, and pre-cancerous cells can evolve into neoplastic cells through the acquisition of somatic mutations. This book is written by international leading scientists in the field of genome stability. Chapters are devoted to genome stability and anti-cancer drug targets, histone modifications, chromatin factors, DNA repair, apoptosis and many other key areas of research. The chapters give insights into the newest development of the genome stability and human diseases and bring the current understanding of the mechanisms leading to chromosome instability and their potential for clinical impact to the reader.
Author: Uwe M. Martens
Publisher: Springer Science & Business Media
ISBN: 3642012221
Category : Medical
Languages : en
Pages : 242
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Book Description
Extensive research into the molecular mechanisms of cancer disease has heralded a new age of targeted therapy. In malignant cells, key proteins that are crucial to tumor growth and survival are now being targeted directly with rationally designed inhibitors. Apart from monoclonal antibodies, small molecule therapeutics such as oncogenic protein kinase inhibitors are attracting a vast amount of investigational attention. This textbook, written by acknowledged experts, provides a broad overview of the small molecules currently used for the treatment of malignant diseases and discusses interesting novel compounds that are in the process of clinical development to combat cancer.
Author: Richard B. Silverman
Publisher: Elsevier
ISBN: 0080513379
Category : Science
Languages : en
Pages : 650
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Book Description
Standard medicinal chemistry courses and texts are organized by classes of drugs with an emphasis on descriptions of their biological and pharmacological effects. This book represents a new approach based on physical organic chemical principles and reaction mechanisms that allow the reader to extrapolate to many related classes of drug molecules. The Second Edition reflects the significant changes in the drug industry over the past decade, and includes chapter problems and other elements that make the book more useful for course instruction. New edition includes new chapter problems and exercises to help students learn, plus extensive references and illustrations Clearly presents an organic chemist's perspective of how drugs are designed and function, incorporating the extensive changes in the drug industry over the past ten years Well-respected author has published over 200 articles, earned 21 patents, and invented a drug that is under consideration for commercialization
