Synthesis and Evaluation of Aza-peptide Carbonyl Derivatives PDF Download
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Author: Leilani Milagros Lotti Diaz
Publisher:
ISBN:
Category : Multiple myeloma
Languages : en
Pages :
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Book Description
The proteasome is central to cellular protein regulation by degrading proteins conjugated to multiple units of the polypeptide ubiquitin. Due to their involvement in the regulation of apoptosis in cells and their abundance in multiple myeloma cells (MM), the proteasome has become a target for cancer treatment. Aza-peptide inhibitors are a new class of inhibitors designed to inhibit the proteasome and other proteases where a P1-amino acid and an electrophilic warhead comprise the potential therapeutic. Previous inhibitors of this type exhibited competitive inhibition of the 20S proteasome with Ki values in the micromolar range for in vitro studies and an IC50 value of 10–50 μM when screened against multiple myeloma and natural killer cell lines.49 In this thesis we present the synthesis and initial SAR studies of different sequences of proteasome-specific aza-peptide inhibitors with ketones and Michael acceptor warheads. We also present the tunability of these inhibitors by designing and synthesizing caspase-6 specific inhibitors. Our goals are to improve the potency and selectivity of aza-peptide inhibitors for optimal selectivity to their target enzymes.
Author: Leilani Milagros Lotti Diaz
Publisher:
ISBN:
Category : Multiple myeloma
Languages : en
Pages :
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Book Description
The proteasome is central to cellular protein regulation by degrading proteins conjugated to multiple units of the polypeptide ubiquitin. Due to their involvement in the regulation of apoptosis in cells and their abundance in multiple myeloma cells (MM), the proteasome has become a target for cancer treatment. Aza-peptide inhibitors are a new class of inhibitors designed to inhibit the proteasome and other proteases where a P1-amino acid and an electrophilic warhead comprise the potential therapeutic. Previous inhibitors of this type exhibited competitive inhibition of the 20S proteasome with Ki values in the micromolar range for in vitro studies and an IC50 value of 10–50 μM when screened against multiple myeloma and natural killer cell lines.49 In this thesis we present the synthesis and initial SAR studies of different sequences of proteasome-specific aza-peptide inhibitors with ketones and Michael acceptor warheads. We also present the tunability of these inhibitors by designing and synthesizing caspase-6 specific inhibitors. Our goals are to improve the potency and selectivity of aza-peptide inhibitors for optimal selectivity to their target enzymes.
Author: Mark Edward Hediger
Publisher:
ISBN:
Category :
Languages : en
Pages : 440
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Book Description
Author: Tom O'Brien
Publisher: CRC Press
ISBN: 9781420045413
Category : Science
Languages : en
Pages : 312
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Book Description
Presents the Therapeutic Potential for Caspase Inhibitors: Present and Future Caspases represent one of the most specific protease families described to date. These extremely important enzymes are crucial to the destruction of aberrant cells – the body’s self-protection mechanism for warding off the growth of abnormal cells, many of which can promote cancer. Design of Caspase Inhibitors as Potential Clinical Agents introduces cutting-edge evidence regarding caspases’ role in pro-inflammatory responses. New research now shows that the inhibition of caspase function is a critical component for the treatment of many diseases, including: Arthritic and neurological disorders Lung disease Hereditary fever syndromes Inflammatory bowel and skin diseases Sepsis Liver fibrosis Outlines Efforts to Develop Molecule Inhibitors for Caspase Activity Transformation Under the editorial guidance of authoritative inflammatory disease, small molecule discovery, and apoptosis researchers, the book organizes the wide array of caspase literature into one convenient resource. It also summarizes the relative difficulty of transitioning a caspase small molecule inhibitor from the lab to the clinic and suggests approaches to circumvent this difficulty. Taking a novel, yet core approach to disease treatment, this seminal work sets the stage to combat a slew of debilitating diseases through groundbreaking drug development.
Author: Peter V. Bozhkov
Publisher: Humana
ISBN: 9781493903566
Category : Science
Languages : en
Pages : 0
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Book Description
Caspases, Paracaspases, and Metacaspacses: Methods and Protocols is a collection of laboratory protocols covering current methods that are employed to measure and detect activities of these proteases in diverse biological systems, ranging from unicellular organisms to mammals. Broken into two parts, the first part focuses on methods to measure, detect, and inhibit activation and activity of a subset of or specific caspases in vitro and in several model systems and organisms, primarily in the context of programmed cell death. The second part of the book provides experimental protocols for purification and in vitro and in vivo analysis of yeast, protozoan and plant metacaspases, as well as of a human paracaspase MALT1. Written in the highly successful Methods in Molecular Biology series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Authoritative and practical, Caspases, Paracaspases, and Metacaspacses: Methods and Protocols seeks to aid scientists easy-to-follow techniques.
Author: Shahid Ul-Islam
Publisher: John Wiley & Sons
ISBN: 1119640342
Category : Science
Languages : en
Pages : 434
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Book Description
In view of their promising biological and pharmaceutical activities, natural product inspired and heterocyclic compounds have recently gained a reputation in the field of medicinal chemistry. Over the past decades, intensive research efforts have been ongoing to understand the synthesis, biochemistry and engineering involved in their preparation and action mechanisms. Several novel natural product derivatives, heterocyclic and other synthetic compounds, have been reported to have shown interesting biological activities including anticancer, antimicrobial, anti-inflammatory, anti-glycemic, anti-allergy and antiviral etc. Chemistry of Biologically Potent Natural Products and Synthetic Compounds provides up-to-date information on new developments and most recent medicinal applications of the natural products and derivatives, as well as the chemistry and synthesis of heterocyclic and other related compounds.
Author: N. Leo Benoiton
Publisher: CRC Press
ISBN: 1420027697
Category : Medical
Languages : en
Pages : 304
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Book Description
Chemistry of Peptide Synthesis is a complete overview of how peptides are synthesized and what techniques are likely to generate the most desirable reactions. Incorporating elements from the author's role of Career Investigator of the Medical Research Council of Canada and his extensive teaching career, the book emphasizes learning rather th
Author: Aleksey Kuznetsov
Publisher: BoD – Books on Demand
ISBN: 1839681799
Category : Science
Languages : en
Pages : 148
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Book Description
Azoles are a broad and promising class of five-membered heterocyclic compounds containing from one up to five nitrogen atom(s) that can also contain sulfur or oxygen atoms. Widely used as potent antifungal agents, various azole derivatives have also demonstrated many other promising biological properties. This book covers studies of several types of thiazole-based heterocyclic scaffolds, the development of 4-thiazolidinone and thiazole derivatives with heterocyclic fragments as potential candidates for new drugs against trypanosomiasis, numerous synthetic approaches for the synthesis of 1,2,3-triazoles, the application of N-azole, N,S-azole, and N,O-azole as well as their derivatives as retarders of metallic corrosion, and the integration of azoles in materials used for renewable energy processing and applications and wood treatment.
Author: E.James Petersson
Publisher: Elsevier
ISBN: 0128212535
Category : Science
Languages : en
Pages : 640
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Book Description
Methods in Enzymology series, highlights new advances in the field, with this new volume presenting interesting chapters. Each chapter is written by an international board of authors. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Methods of Enzymology series Updated release includes the latest information on the Synthetic and Enzymatic Modifications of the Peptide Backbone
Author: Ming Ming Chen Hammond
Publisher:
ISBN:
Category :
Languages : en
Pages : 436
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Book Description
Author: Ved Srivastava
Publisher: Royal Society of Chemistry
ISBN: 1782627324
Category : Medical
Languages : en
Pages : 589
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Book Description
With potentially high specificity and low toxicity, biologicals offer promising alternatives to small-molecule drugs. Peptide therapeutics have again become the focus of innovative drug development efforts backed up by a resurgence of venture funds and small biotechnology companies. What does it take to develop a peptide-based medicine? What are the key challenges and how are they overcome? What are emerging therapeutics for peptide modalities? This book answers these questions with a holistic story from molecules to medicine, combining the themes of design, synthesis and clinical applications of peptide-based therapeutics and biomarkers. Chapters are written and edited by leaders in the field from industry and academia and they cover the pharmacokinetics of peptide therapeutics, attributes necessary for commercially successful metabolic peptides, medicinal chemistry strategies for the design of peptidase-resistant peptide analogues, disease classes for which peptide therapeutic are most relevant, and regulatory issues and guidelines. The critical themes covered provide essential background information on what it takes to develop peptide-based medicine from a chemistry perspective and views on the future of peptide drugs. This book will be a valuable resource not only as a reference book for the researcher engaged in academic and pharmaceutical setting, from basic research to manufacturing and from organic chemistry to biotechnology, but also a valuable resource to graduate students to understand discovery and development process for peptide-based medicine.
