DNA-targeting Molecules as Therapeutic Agents PDF Download

Author: Michael J. Waring
Publisher: Royal Society of Chemistry
ISBN: 1782629920
Category : Medical
Languages : en
Pages : 432

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Book Description
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.

Author: Pamela Greenwell
Publisher: John Wiley & Sons
ISBN: 9780470725146
Category : Science
Languages : en
Pages : 264

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Book Description
"This book should be useful to lecturers who teach senior undergraduates, graduate students, and students in the biomedical sciences in general. More globally, Greenwell and McCulley's book should encourage academicians of any stripe who for some time have been honing their lectures in a niche subject area to turn their courses into textbooks." –Biochemistry and Molecular Biology Education Molecular therapeutics refers to the developments in molecular biology that are focused on treating disease with new molecular-based drugs. By taking advantage of recent advances and increased understanding in the field of human genetics, this book provides essential background knowledge and key literature on a broad range of novel approaches and disciplines. These include making recombinant proteins, xenotransplantation gene therapy and therapeutic cloning. Molecular Therapeutics: 21st Century Medicine describes the techniques - including their associated benefits, problems, pitfalls - and discusses their applicability with respect to treating microbial, inherited, multifactoral and acquired diseases. The book also pays specific attention to the ethical issues associated with this new field. Cutting-edge topics and clinically relevant materials engage and maintain student interest Self-assessment questions are included throughout the book Features an additional web site, with a web forum, regular updates and PowerPoint slides of figures from the book Molecular Therapeutics: 21st Century Medicine is a comprehensive, accessible and engaging guide to the rapidly developing field of molecular therapeutics. It is essential reading for all students in this area of research and also of interest for health professionals involved in these novel therapies.

Author: Michael J Waring
Publisher: Royal Society of Chemistry
ISBN: 1788014286
Category : Science
Languages : en
Pages : 432

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Book Description
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.

Author: Lara Scheherazade Milane
Publisher: CRC Press
ISBN: 1000505936
Category : Science
Languages : en
Pages : 511

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Book Description
We have surpassed the omics era and are truly in the Age of Molecular Therapeutics. The fast-paced development of SARS-CoV-2 vaccines, such as the mRNA vaccines encoding the viral spike protein, demonstrated the need for and capability of molecular therapy and nanotechnology-based solutions for drug delivery. In record speed, the SARS-CoV-2 viral RNA genome was sequenced and shared with the scientific community, allowing the rapid design of molecular therapeutics. The mRNA vaccines exploit the host cell endoplasmic reticulum to produce viral spike proteins for antigen presentation and recognition by the innate and adaptive immune system. Lipid nanoparticles enable the delivery of the fragile, degradation-sensitive nucleic acid payloads. Molecular-based therapeutics and nanotechnology solutions continue to drive the scientific and medical response to the COVID-19 pandemic as new mRNA, DNA, and protein-based vaccines are developed and approved and the emergency use approved vaccines are rapidly manufactured and distributed throughout the globe. The need for molecular therapies and drug delivery solutions is clear, and as these therapies progress and become more specialized there will be important advancements in organelle targeting. For example, using organelle targeting to direct lipid nanoparticles with mRNA payloads to the endoplasmic reticulum would increase the efficacy of mRNA vaccines, reducing the required dose and therefore the biomanufacturing demand. Likewise, improving the delivery of DNA therapeutics to the nucleus would improve efficacy. Organelles and molecules have always been drug targets, but until recently we have not had the tools or capability to design and develop such highly specific therapeutics. Organelle targeting has far-reaching implications. For example, mitochondria are central to both energy production and intrinsic apoptosis. Effectively targeting and manipulating mitochondria has therapeutic applications for diseases such as myopathies, cancer, neurodegeneration, progerias, diabetes, and the natural aging process. The SARS-CoV-2 vaccines that exploit the endoplasmic reticulum (for mRNA vaccines) and the nucleic translational process (DNA vaccines) attest to the need for organelle and molecular therapeutics. This book covers the status, demand, and future of organelle- and molecularly targeted therapeutics that are critical to the advancement of modern medicine. Organelle and molecular targeting is the drug design and drug delivery approach of today and the future; understanding this approach is essential for students, scientists, and clinicians contributing to modern medicine.

Author: M. Palumbo
Publisher: Elsevier
ISBN: 008054455X
Category : Science
Languages : en
Pages : 297

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Book Description
In this volume the entire focus is devoted to the macromolecule target specificity of DNA interactive developmental therapeutic agents of current interest. A brief introduction to DNA interactive anticancer agents is included for readers who may benefit from an overview surrounding the developments that have contributed to our general understanding of this field. The following nine chapters have been carefully chosen so that they describe topics which are at the forefront of development in DNA-targeted cancer chemotherapy. Issues that have been addressed include the mechanisms of selective DNA topoisomerase I and II poisoning by antitumor agents (Chapters 1 and 2), sequence-specific recognition of DNA by groove-binding drugs and drug-conjugates (Chapters 3 and 4), recent developments in nitrogen mustard alkylating agents and their potential use for antibody-directed enzyme-prodrug therapy (Chapter 5), nonclassical platinum anticancer complexes, including dinuclear and trans-platinum derivatives (Chapter 6), DNA cleaving antitumor chromoproteins containing reactive enediyne moieties, which exhibit interesting free-radical chemistry along with selective targeting (Chapter 7), the potential of new sequence-specific antisense and antigene therapy in oncology (Chapter 8), and finally the conceivable chemotherapeutic use of mimetics of the DNA structure, obtained by substitution of the sugar-phosphate natural chain with a peptide backbone, the so-called peptide nucleic acids (Chapter 9). Important approaches being currently investigated for selective cancer treatment, such as gene therapy and immunochemotherapy, are not discussed in this volume since they fall beyond its scope.

Author: Laura Sesma Sanz
Publisher:
ISBN:
Category :
Languages : en
Pages : 251

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Book Description
Cancer is a very heterogeneous disease with a multitude of different facets. However, even different types of cancer share a set of characteristics that can be exploited for therapeutic purposes. In our group we are interested in DNA damage and repair, particularly in the context of cancer, since genomic instability is considered one of the “Hallmarks of Cancer”. Homologous Recombination (HR) is a mechanism used by cells to repair Double-Strand Breaks, the most harmful type of DNA damage. Deficiencies in this pathway of DNA repair results in increased genomic instability and has been observed in a wide variety of tumours, notably in ovarian and breast cancer. The events most commonly associated with HR defects are genetic alterations in HR related genes such as BRCA1, BRCA2 and the more recently identified PALB2. The concept of synthetic lethality describes the incompatibility or lethality of two simultaneous events that are individually tolerable. Cancer research is taking advantage of this idea to develop new targeted treatments. The most important success of synthetic lethality-based therapy development is the case of PARP inhibitors. It was observed that inhibition of PARP-1, an abundant protein involved in many cellular processes, including DNA repair, is synthetically lethal with defects in Homologous Recombination. Therefore, PARP inhibitors were developed to specifically target HR-deficient tumours while sparing normal HR-proficient tissues. Nevertheless, as with most drugs, many patients develop resistance to PARP inhibitors, which can lead to disease recurrence, thus highlighting the need for alternative treatment options. Recent research has focused not only on finding new synthetic lethal interactions but also on developing new combinations of molecules to potentiate their effect and both prevent and counteract resistances to drugs. Following this idea, the main objective of my doctoral work was to find new potential treatments for HR-deficient tumours, alone or in combination with PARP inhibitors. Within this project, we also developed a new in cellulo screen system, based on analyzing the effects of the studied compounds on cell populations with different HR capacities. We stably transfected HR-proficient and deficient cell lines to express either red or green fluorescent proteins, respectively, and co-cultured them with more than 1000 drugs of a library of compounds. We identified CB1954, previously studied as a prodrug, to specifically target HR-deficient cells. Interestingly, CB1954 synergizes with PARP inhibitors in both HR-deficient and proficient cells, thus constituting a promising combination with interesting potential. Additionally, we identified synergy between PARP inhibition (Talazoparib) and type I PRMT inhibition (MS023) in MTAP-negative NSCLC and ovarian cancer cells, both PARPi sensitive and resistant. Both combinations need further examination to better characterize their mechanisms of action and identify the biomarkers for sensitivity and resistance to the treatments. We are currently studying the effects of CB1954+PARPi on cell fate and, since we have confirmed the effects of the drugs and the synergy in 3D cultured cells, we are testing the combination in ovarian cancer xenograft mouse models. In summary, we have developed a new fluorescence-based method to screen for compounds having a synthetic lethal effect, which could be adapted to the study of other pathologies. We have also identified and tested two new compound combinations that could potentially be applied to the treatment of tumours resistant to PARP inhibitors.

Author: Toshiwo Andoh
Publisher: Springer Science & Business Media
ISBN: 9780306477447
Category : Medical
Languages : en
Pages : 224

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Book Description
This volume commemorates the 30th anniversary of the discovery in 1971 of the first DNA topoisomerases, i.e topoisomerase I in E. coli, then provisionally named `omega' protein, by the pioneering work of Jim Wang at Harvard University, who has contributed an article to this volume: `Reflections on an accidental discovery' of the enzyme. Many kinds of topoisomerase have since been found from type I through to type VI in a variety of organisms ranging from viruses to higher eukaryote mammals. The wide distribution of enzymes in various forms of life implies that the DNA topoisomerase is essential for life. In the mid 80's type I and II enzymes were found to be the intracellular targets of a number of efficacious anticancer drugs such as doxorubicin, mitoxantrone, etoposide and camptothecin as a result of a continued efforts of many investigators, especially Leroy Liu and his collaborators at Johns Hopkins University. Readers will find a series of chapters written by researchers actively engaged in the expanding field of topoisomerase and their inhibitors. The series of chapters cover review articles on pharmacology and the molecular mechanism of topoisomerase I- and II-targeting anticancer drugs in mammals and in the yeast Saccharomyces cerevisiae, which has proved to be a superb model organism for studies of anticancer drugs. This volume compiles up-to-date information on the topoisomerase-targeting compounds in clinical and preclinical development as a useful and important reference book for students and researchers in the field of pharmacology, toxicology, oncology and molecular biology.

Author: Yizhu Li
Publisher:
ISBN:
Category :
Languages : en
Pages : 0

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Book Description
The DNA molecule stands at the center of cancer origin and treatment. Cancer cells are addicted to DNA mutations and DNA replication, therapeutic non-responders are often based on the rate of mutations and ability to replicate DNA. Conversely, DNA, being the most vulnerable spot of a tumor, is also the main target for chemotherapies. The in-depth understanding of cellular processes upon errors in the DNA genetic code is therefore crucial for designing new chemotherapeutic drugs and new combinations of drugs; specifically, it is the main endeavor to induce and exacerbate DNA damage in cancer...

Author: Robert C. Bast, Jr.
Publisher: John Wiley & Sons
ISBN: 111900084X
Category : Medical
Languages : en
Pages : 2004

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Book Description
Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates

Author: John Dickenson
Publisher: John Wiley & Sons
ISBN: 1118451953
Category : Medical
Languages : en
Pages : 675

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Book Description
This textbook provides a fresh, comprehensive and accessible introduction to the rapidly expanding field of molecular pharmacology. Adopting a drug target-based, rather than the traditional organ/system based, approach this innovative guide reflects the current advances and research trend towards molecular based drug design, derived from a detailed understanding of chemical responses in the body. Drugs are then tailored to fit a treatment profile, rather than the traditional method of ‘trial and error’ drug discovery which focuses on testing chemicals on animals or cell cultures and matching their effects to treatments. Providing an invaluable resource for advanced under-graduate and MSc/PhD students, new researchers to the field and practitioners for continuing professional development, Molecular Pharmacology explores; recent advances and developments in the four major human drug target families (G-protein coupled receptors, ion channels, nuclear receptors and transporters), cloning of drug targets, transgenic animal technology, gene therapy, pharmacogenomics and looks at the role of calcium in the cell. Current - focuses on cutting edge techniques and approaches, including new methods to quantify biological activities in different systems and ways to interpret and understand pharmacological data. Cutting Edge - highlights advances in pharmacogenomics and explores how an individual’s genetic makeup influences their response to therapeutic drugs and the potential for harmful side effects. Applied - includes numerous, real-world examples and a detailed case-study based chapter which looks at current and possible future treatment strategies for cystic fibrosis. This case study considers the relative merits of both drug therapy for specific classes of mutation and gene therapy to correct the underlying defect. Accessible - contains a comprehensive glossary, suggestions for further reading at the end of each chapter and an associated website that provides a complete set of figures from within the book.