Development of Alpha/beta-peptides as Fusion Inhibitors of HIV and Agonists of Glucagon-like Peptide-1 Receptor (glp-1r) PDF Download
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Languages : en
Pages : 0
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Book Description
There are many strategies that target biomedically important protein-protein interactions, based on small molecules, antibodies, and peptides. Peptides have the advantages of selectively targeting the protein of interest through a broad distribution of multiple interactions, unlike small molecules, and being relatively small in size, unlike an antibody. However, peptides have the disadvantage of being rapidly degraded by proteases. The Gellman group has developed strategies to incorporate beta-amino acids into biomedically relevant peptides to create alpha/beta-peptides that have similar biological activity to the natural alpha-peptide but increased protease resistance. The first part of my thesis focuses on development of alpha/beta-peptides as inhibitors of HIV infection. The protein gp41 is a surface protein on the HIV virus that is responsible for fusion of the viral membrane to the host cell membrane. Helical alpha-peptides, based on the viral sequence, are potent infection inhibitors because they bind to gp41 and inhibit the fusion mechanism. I describe two design strategies, one involving cyclic beta-residue constraints and the other involving electrostatic side chain interactions of beta-residues, to preorganize a helical alpha/beta-peptide conformation. Both of these design strategies have proven effective in creating alpha/beta-peptides that are as active as a prototype alpha-peptide in cell-based HIV infectivity assays and more resistant to proteolysis in in vitro assays. The alpha/beta-peptides are also used as tools to probe the binding interface between inhibitory peptides and the target structure formed by gp41. The second part of my thesis focuses on development of alpha/beta-peptides as agonists of the GLP-1 receptor (GLP-1R). The natural agonist of GLP-1R, glucagon-like peptide-1 (GLP-1), has received attention as a therapeutic agent for type 2 diabetes. GLP-1 has a short half-life in the bloodstream (two minutes). My goal was to increase the biological stability of GLP-1 by incorporating unnatural beta-residues and alpha-residues into the sequence. I describe the design strategy for an effective GLP-1 analogue and the performance of this analogue in cell-based assays and animal studies.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
There are many strategies that target biomedically important protein-protein interactions, based on small molecules, antibodies, and peptides. Peptides have the advantages of selectively targeting the protein of interest through a broad distribution of multiple interactions, unlike small molecules, and being relatively small in size, unlike an antibody. However, peptides have the disadvantage of being rapidly degraded by proteases. The Gellman group has developed strategies to incorporate beta-amino acids into biomedically relevant peptides to create alpha/beta-peptides that have similar biological activity to the natural alpha-peptide but increased protease resistance. The first part of my thesis focuses on development of alpha/beta-peptides as inhibitors of HIV infection. The protein gp41 is a surface protein on the HIV virus that is responsible for fusion of the viral membrane to the host cell membrane. Helical alpha-peptides, based on the viral sequence, are potent infection inhibitors because they bind to gp41 and inhibit the fusion mechanism. I describe two design strategies, one involving cyclic beta-residue constraints and the other involving electrostatic side chain interactions of beta-residues, to preorganize a helical alpha/beta-peptide conformation. Both of these design strategies have proven effective in creating alpha/beta-peptides that are as active as a prototype alpha-peptide in cell-based HIV infectivity assays and more resistant to proteolysis in in vitro assays. The alpha/beta-peptides are also used as tools to probe the binding interface between inhibitory peptides and the target structure formed by gp41. The second part of my thesis focuses on development of alpha/beta-peptides as agonists of the GLP-1 receptor (GLP-1R). The natural agonist of GLP-1R, glucagon-like peptide-1 (GLP-1), has received attention as a therapeutic agent for type 2 diabetes. GLP-1 has a short half-life in the bloodstream (two minutes). My goal was to increase the biological stability of GLP-1 by incorporating unnatural beta-residues and alpha-residues into the sequence. I describe the design strategy for an effective GLP-1 analogue and the performance of this analogue in cell-based assays and animal studies.
Author: Zigang Li
Publisher: John Wiley & Sons
ISBN: 3527343423
Category : Science
Languages : en
Pages : 242
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Book Description
An important and timely guide to the progress being made on constrained helical peptides Constraint helical peptides have emerged as a solution to target previously undruggable protein-protein interactions, which feature large and complex surfaces. Cyclized Helical Peptides: Synthesis, Properties and Therapeutic Applications offers a review of the most current methodologies of constructing constrained helices. The authors noted experts on the topic include the information on the fundamental features of cyclized helical peptides and discuss their limitations. The book summarizes and explores the effects of chemical methods constructing helical peptides on helicity, binding affinity, cell penetration, and nonspecific toxicity. The book examines the therapeutic applications of the constraint helices and includes comparison with existing small molecule modulators or antibodies. Designed as a useful resource for both those outside and inside the field. Those new to the field will find a comprehensive introduction to cyclized helical peptide and those inside the field will find a deeper understanding of the topic. This important book: Offers a practical introduction to constrained helical peptides Includes all aspects of constrained helical peptides Includes information on the most recent methods that have emerged Presents a guide to help solve practical problems in the field Written for academics, pharmaceutical professional, Cyclized Helical Peptides is a comprehensive guide to the developments of constrained helical peptides.
Author: C. Robin Ganellin
Publisher: Academic Press
ISBN: 0123977703
Category : Science
Languages : en
Pages : 469
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Book Description
Introduction to Biological and Small Molecule Drug Research and Development provides, for the first time, an introduction to the science behind successful pharmaceutical research and development programs. The book explains basic principles, then compares and contrasts approaches to both biopharmaceuticals (proteins) and small molecule drugs, presenting an overview of the business and management issues of these approaches. The latter part of the book provides carefully selected real-life case studies illustrating how the theory presented in the first part of the book is actually put into practice. Studies include Herceptin/T-DM1, erythropoietin (Epogen/Eprex/NeoRecormon), anti-HIV protease inhibitor Darunavir, and more. Introduction to Biological and Small Molecule Drug Research and Development is intended for late-stage undergraduates or postgraduates studying chemistry (at the biology interface), biochemistry, medicine, pharmacy, medicine, or allied subjects. The book is also useful in a wide variety of science degree courses, in post-graduate taught material (Masters and PhD), and as basic background reading for scientists in the pharmaceutical industry. For the first time, the fundamental scientific principles of biopharmaceuticals and small molecule chemotherapeutics are discussed side-by-side at a basic level Edited by three senior scientists with over 100 years of experience in drug research who have compiled the best scientific comparison of small molecule and biopharmaceuticals approaches to new drugs Illustrated with key examples of important drugs that exemplify the basic principles of pharmaceutical drug research and development
Author:
Publisher: Academic Press
ISBN: 0128191295
Category : Science
Languages : en
Pages : 310
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Book Description
Chemical and Synthetic Biology Approaches to Understand Cellular Functions - Part C, Volume 633, the latest release in the Methods in Enzymology series, continues the legacy of this premier serial. This release includes sections on Next generation probes for molecular imaging in cells, Competitive binding assay for biotin and biotin derivatives, based on avidin and biotin-4-fluorescein, Converting avidin to bind ligands other than biotin, especially steroids, Chemoenzymatic Labeling Strategy, Engineered Siderophores, Small molecules to inhibit bacterial population behavior, NMR tube bioreactor, Small molecule controlled RAS activation system, Small molecule regulated Cas9, the Design and application of synthetic receptors, and much more. Contains the authority of authors who are leaders in their field Provides a comprehensive source on new methods and research in enzymology
Author: Biswanath Dinda
Publisher: Springer
ISBN: 3030055752
Category : Science
Languages : en
Pages : 296
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Book Description
In this book, the author provides expert analysis on naturally occurring iridoids, their chemistry and their distribution in plants and insects. Particular attention is given to the pharmacology of iridoids and their prospective applications in pharmaceutical and agricultural industries. Iridoids are found in a wide variety of plants and some insects, and they are structurally derived from monoterpenoid natural products. In the first two chapters of this book, the author describes the iridoids classification, occurrence and distribution in plants and insects. The following chapters cover different chromatographic and spectroscopic techniques that can be used to identify and quantify iridoids in herbal formulations, and also the biosynthesis of iridoids, in which the reader will discover a metabolomics and transcriptomics analysis to identify the genes involved in the biosynthesis. The final chapters provide insights on several pharmacological activities of iridoids, their physiological role in insects, pharmacokinetics in mammals, insects and microorganisms, and their applications in medicine and agriculture. This book will engage students and researchers interested in the chemistry of natural products, and it will also appeal to medicinal chemists and practitioners working in the design of new herbal drugs with bioactive pure iridoids.
Author: Iqbal Ramzan
Publisher: John Wiley & Sons
ISBN: 1119564654
Category : Medical
Languages : en
Pages : 328
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Book Description
A comprehensive primer and reference, this book provides pharmacists and health practitioners the relevant science and policy concepts behind biologics, biosimilars, and biobetters from a practical and clinical perspective. Explains what pharmacists need to discuss the equivalence, efficacy, safety, and risks of biosimilars with physicians, health practitioners, and patients about Guides regulators on pragmatic approaches to dealing with these drugs in the context of rapidly evolving scientific and clinical evidence Balances scientific information on complex drugs with practical information, such as a checklist for pharmacists
Author: Andrew P. Zbar
Publisher: Springer Science & Business Media
ISBN: 9781852334826
Category : Medical
Languages : en
Pages : 486
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Book Description
An understanding of the complex workings of the immune system is essential for all surgeons. Immune responses play a crucial part in the way human body reacts to infection and trauma. Immunology for Surgeons contains a high-level discussion of this difficult clinical area. The text looks at tumor immunobiology and immunotherapy as well as the worldwide results of various clinical trials. The topics discussed focus on relevant immunological and molecular biological trends for future treatment of complex surgical disease. The main objective of the text is to render a difficult area accessible for the postgraduate surgical trainee and established surgeon who is interested in immunology.
Author: James E. Barrett
Publisher: Springer Nature
ISBN: 3030353621
Category : Medical
Languages : en
Pages : 466
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Book Description
Celebrating 100 years of HEP, this volume will discuss key pharmacological discoveries and concepts of the past 100 years. These discoveries have dramatically changed the medical treatment paradigms of many diseases and these concepts have and will continue to shape discovery of new medicinies. Newly evolving technologies will similarly be discussed as they will shape the future of the pharmacology and, accordingly, medical therapy.
Author: Nihal Thomas
Publisher: JAYPEE BROTHERS PUBLISHERS
ISBN: 9350905973
Category : Health & Fitness
Languages : en
Pages : 467
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Book Description
The Sixth Edition of A Practical Guide to Diabetes Mellitus offers a unique combination of rigorous pathophysiology with very practical approaches to diabetes prevention and control. This outstanding textbook will equip a cadre of doctors and other health care professionals to deliver high quality care to vulnerable populations around India and far beyond. Based on research as well as clinical practice, the text describes diabetes in relation to physiology, ocular, cardiovascular, neuropathy, pregnancy, emergencies, childhood diabetes, etc. Each chapter beings with a brief outline of the disease concerned followed by introduction, definition/terminology, classification, treatment, conclusion and ending with set of question for self-assessment. Covers step wise images describes insulin administration in subcutaneous and using pen devices in the chapter: Insulin therapy: practical aspects. Feet, Footcare and Neuroarthropathy chapter deals with etiology and pathophysiology and is divided into three parts: Ulceration, Neuroarthropathy and Peripheral Artery Occlusive(PAD) diseases. Infection in diabetes chapter focuses on infection related to head and neck, genitourinary, skin and soft tissue, pulmonology and abdominal. Recent advances includes application of new drugs like Taspoglutide, Albiglutide, Lixisenatide, Newer DPP-IV inhibitors, along with new insulin receptor activators, PPAR agonists, new hepatic targets for glycemic control in diabetes. This book contains more than 300 coloured images and illustrations, 40 clinical cases, 50 questions for quick revision along with answers to the self-assessments question given at the end of book."
Author: Ali Tavassoli
Publisher: Royal Society of Chemistry
ISBN: 178801569X
Category : Science
Languages : en
Pages : 357
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Book Description
Protein-protein interactions (PPI) are at the heart of the majority of cellular processes, and are frequently dysregulated or usurped in disease. Given this central role, the inhibition of PPIs has been of significant interest as a means of treating a wide variety of diseases. However, there are inherent challenges in developing molecules capable of disrupting the relatively featureless and large interfacial areas involved. Despite this, there have been a number of successes in this field in recent years using both traditional drug discovery approaches and innovative, interdisciplinary strategies using novel chemical scaffolds. This book comprehensively covers the various aspects of PPI inhibition, encompassing small molecules, peptidomimetics, cyclic peptides, stapled peptides and macrocycles. Illustrated throughout with successful case studies, this book provides a holistic, cutting-edge view of the subject area and is ideal for chemical biologists and medicinal chemists interested in developing PPI inhibitors.
