Sites Of Interaction Between Calcitonin Family Peptides And Their Receptors
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Sites Of Interaction Between Calcitonin Family Peptides And Their Receptors
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Author : Tao Qi
language : en
Publisher:
Release Date : 2011
Sites Of Interaction Between Calcitonin Family Peptides And Their Receptors written by Tao Qi and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with Amylin categories.
"The calcitonin-family of peptides comprises calcitonin, amylin, calcitonin gene-related peptides (CGRPs), adrenomedullin (AM) and AM2. Their receptors are calcitonin receptorlike receptor (CLR) or calcitonin receptor (CTR) and receptor activity-modifying protein (RAMP) complexes. RAMP1 with CLR constitutes the CGRP receptor whereas RAMP2 or 3 with CLR generates the AM receptors. Amylin receptors are formed from CTR interactions with RAMPs. The association of RAMPs with CLR or CTR can alter receptor trafficking, pharmacology or/and signalling capabilities. Despite the broad pharmacological potential as drug targets for treatments of diseases such as diabetes, migraine and osteoporosis, the calcitonin peptide family receptors are not fully characterised. This is mainly due to the difficulty in the structural determination and the complexity of the interaction system. To generate drugs that target these receptors, a clearer understanding of the role of each receptor component in peptide binding is needed. In the thesis, structure-function relationships of residues or regions in the extracellular N termini of RAMPs were determined aiming to identify residues or regions that are important for ligand to receptor interactions for the calcitonin family peptides. The data generated have emphasised the importance of helices 2 and 3 of RAMP to peptide to receptor interactions. In particular, E74 of RAMP3 has been demonstrated to be crucial for high affinity binding and high potency response of AM at the AM2 receptor. In addition, a naturally occurring variant of the human CTR lacking the N-terminal 47 amino acids has been characterised in this thesis. For the first time, it has been shown that this truncated variant is still able to form a functional amlyin receptor with RAMP1 at the cell surface. The observation of reduced potency for some peptide ligands at the truncated CTR suggests that the truncated region may contain some residues that are involved in the interactions for these peptides. In summary, the findings in this thesis have contributed to our understanding of the ligand to receptor interactions for the calcitonin family peptides. Residues and regions identified in this thesis could potentially provide some targeting points for future investigations for rational drug design"--Abstract.
The Calcitonin Gene Related Peptide Family
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Author : Deborah L. Hay
language : en
Publisher: Springer Science & Business Media
Release Date : 2009-10-03
The Calcitonin Gene Related Peptide Family written by Deborah L. Hay and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009-10-03 with Medical categories.
In 1925, J. B. Collip (1925) reported that extracts of parathyroid gland contained an activity that raised calcium levels in the blood of parathyroidectomized animals, and suggested that this was due to a hormone produced in the parathyroid gland. The story of parathyroid hormone discovery was indicative of ever-increasing sophistication in sample preparation and protein isolation techniques. This paper resolved earlier controversies over the function of the parathyroid glands and c- trol of blood calcium. The year 1961 was a banner year for parathyroid research, in which the peptides parathyroid hormone and calcitonin were purified, and in which it was suggested that calcitonin could lower blood calcium (Copp and Cameron 1961). In 1982 it was discovered that in neurons the primary RNA transcript for calcitonin could be alternatively-spliced to give calcitonin gene-reated peptide (CGRP), and shortly thereafter amylin (previously named islet amyloid polyp- tide, IAPP) was identified and shown to have homology to CGRP. Since then a and b CGRP have been delineated and adrenomedullin and intermedin discovered, and this family of homologous peptides has emerged. This family of peptide hormones has a diverse and constantly expanding range of important physiologic functions, including regulation of blood calcium, vascular tension, feeding behavior and pain recognition.
Structure Function Analysis Of Calcitonin And Amylin Receptors
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Author : Joseph John Gingell
language : en
Publisher:
Release Date : 2015
Structure Function Analysis Of Calcitonin And Amylin Receptors written by Joseph John Gingell and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015 with Amylin categories.
The calcitonin receptor (CTR) is a peptide binding family B G protein-coupled receptor (GPCR). CTR alone has high affinity for calcitonin (CT) but when expressed with receptor activitymodifying proteins 1, 2 and 3 (RAMPs) it forms the AMY1, AMY2 and AMY3 receptors, which have increased affinity for amylin and CT gene-related peptide (CGRP). Family B GPCRs have a long N-terminal extracellular domain (ECD) that forms an important part of the peptide binding site. While peptide bound ECD structures are available for several family B GPCRs, there is no structural information available on the CTR. The precise binding sites of the peptides CT, amylin and CGRP within the ECD are unknown and it is also unclear if or how the presence of the RAMP changes the peptide binding site to allow high affinity amylin and CGRP binding. In this thesis, site-directed mutagenesis and functional assays were performed on the CTR ECD with the aim of identifying residues involved in peptide interactions. CTR ECD mutants were characterised with CT, CGRP and amylin in the presence and absence of RAMPs, to investigate how RAMPs influence peptide binding. In addition beta amyloid 1-42, was investigated as a potential novel agonist of AMY receptors. The isolated ECDs of the CTR and RAMP1 were also expressed with the aim of characterising them by X-ray crystallography. The mutagenesis data identified CTR ECD residues involved in CT, CGRP and amylin interactions. Interestingly there were differences in CT and amylin interactions with the CTR; alanine mutants W79A, F99A, D101A, F102A, W128A and Y131A, significantly reduced CT potency, however only W79A, F102A and Y131A reduced amylin potency. At the AMY receptors seven receptor mutants; W79A, F99A, D101A, F102A, R126A, W128A and Y131A resulted in a significant decrease in amylin potency, indicating that additional receptor residues become involved in amylin binding when RAMPs are present. This suggests that RAMPs may act indirectly to alter peptide binding at AMY receptors.
The Chemistry And Biology Of Nitroxyl Hno
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Author : Fabio Doctorovich
language : en
Publisher: Elsevier
Release Date : 2016-09-01
The Chemistry And Biology Of Nitroxyl Hno written by Fabio Doctorovich and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-09-01 with Science categories.
The Chemistry and Biology of Nitroxyl (HNO) provides first-of-its-kind coverage of the intriguing biologically active molecule called nitroxyl, or azanone per IUPAC nomenclature, which has been traditionally elusive due to its intrinsically high reactivity. This useful resource provides the scientific basis to understand the chemistry, biology, and technical aspects needed to deal with HNO. Building on two decades of nitric oxide and nitroxyl research, the editors and authors have created an indispensable guide for investigators across a wide variety of areas of chemistry (inorganic, organic, organometallic, biochemistry, physical, and analytical); biology (molecular, cellular, physiological, and enzymology); pharmacy; and medicine. This book begins by exploring the unique molecule’s structure and reactivity, including important reactions with small molecules, thiols, porphyrins, and key proteins, before discussing chemical and biological sources of nitroxyl. Advanced chapters discuss methods for both trapping and detecting nitroxyl by spectroscopy, electrochemistry, and fluorescent inorganic cellular probing. Expanding on the compound’s foundational chemistry, this book then explores its molecular physiology to offer insight into its biological implications, pharmacological effects, and practical issues. Presents the first book on HNO (nitroxyl or azanone), an increasingly important molecule in biochemistry and pharmaceutical research Provides a valuable coverage of HNO’s chemical structure and significant reactions, including practical guidance on working with this highly reactive molecule Contains high quality content from recognized experts in both industry and academia
Encyclopedia Of Bone Biology
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Author :
language : en
Publisher: Academic Press
Release Date : 2020-06-26
Encyclopedia Of Bone Biology written by and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-06-26 with Science categories.
Encyclopedia of Bone Biology, Three Volume Set covers hot topics from within the rapidly expanding field of bone biology and skeletal research, enabling a complete understanding of both bone physiology and its relation to other organs and pathophysiology. This encyclopedia will serve as a vital resource for those involved in bone research, research in other fields that cross link with bone, such as metabolism and immunology, and physicians who treat bone diseases. Each article provides a comprehensive overview of the selected topic to inform a broad spectrum of readers from advanced undergraduate students to research professionals. Chapters also explore the latest advances and hot topics that have emerged in recent years, including the Hematopoietic Niche and Nuclear Receptors. In the electronic edition, each chapter will include hyperlinked references and further readings as well as cross-references to related articles. Incorporates perspectives from experts working within the domains of biomedicine, including physiology, pathobiology, pharmacology, immunology, endocrinology, orthopedics and metabolism Provides an authoritative introduction for non-specialists and readers from undergraduate level upwards, as well as up-to-date foundational content for those familiar with the field Includes multimedia features, cross-references and color images/videos
The Aging Skeleton
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Author : Clifford Rosen
language : en
Publisher: Elsevier
Release Date : 1999-08-19
The Aging Skeleton written by Clifford Rosen and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 1999-08-19 with Medical categories.
The Aging Skeleton is a comprehensive and timely book on all aspects of the skeleton as it ages, including basic mechanisms and pathways as well as pathobiology. Chapters cover general aspects and models of aging, determinants and maintenance of peak bone mass, mechanisms of age-related bone loss, quantifiable manifestations of age-related bone loss, fractures, and therapeutics. Covers all aspects of the aging skeleton in one comprehensive volume Looks at the influence of genetics, nutrition, environment, hormones, and other factors on bone mass Provides a thorough discussion of fractures, one of the major consequences of the aging skeleton Reviews current therapeutic approaches and methods Written by internationally renowned authors and edited by leaders in the field Is the only book available on this subject
Adrenomedullin
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Author : Alfredo Martínez
language : en
Publisher: IOS Press
Release Date : 1998
Adrenomedullin written by Alfredo Martínez and has been published by IOS Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 1998 with Adrenomedullin categories.
Adrenomedullin is a recently discovered peptide hormone which involved in many physiological and pathological processes. This book reviews all the information available on this intriguing molecule, covering topics as diverse as blood pressure regulation, growth of tumours and normal cells, the central nervous system, and comparative studies from sharks to mammals. An international group of experts has contributed to this volume which will be of interest to professionals, researchers, and those who will benefit from a broad review of the literature and the main trends in adrenomedullin research.
Synthesis Of Best Seller Drugs
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Author : Ruben Vardanyan
language : en
Publisher: Academic Press
Release Date : 2016-01-07
Synthesis Of Best Seller Drugs written by Ruben Vardanyan and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-01-07 with Medical categories.
Synthesis of Best-Seller Drugs is a key reference guide for all those involved with the design, development, and use of the best-selling drugs. Designed for ease of use, this book provides detailed information on the most popular drugs, using a practical layout arranged according to drug type. Each chapter reviews the main drugs in each of nearly 40 key therapeutic areas, also examining their classification, novel structural features, models of action, and synthesis. Of high interest to all those who work in the captivating areas of biologically active compounds and medicinal drug synthesis, in particular medicinal chemists, biochemists, and pharmacologists, the book aims to support current research efforts, while also encouraging future developments in this important field. Describes methods of synthesis, bioactivity and related drugs in key therapeutic areas Reviews the main drugs in each of nearly 40 key therapeutic areas, also examining their classification, novel structural features, models of action, and more Presents a practical layout designed for use as a quick reference tool by those working in drug design, development and implementation
Sturkie S Avian Physiology
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Author : Colin G. Scanes
language : en
Publisher: Elsevier
Release Date : 2014-06-30
Sturkie S Avian Physiology written by Colin G. Scanes and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-06-30 with Science categories.
Sturkie's Avian Physiology is the classic comprehensive single volume on the physiology of domestic as well as wild birds. The Sixth Edition is thoroughly revised and updated, and features several new chapters with entirely new content on such topics as migration, genomics and epigenetics. Chapters throughout have been greatly expanded due to the many recent advances in the field. The text also covers the physiology of flight, reproduction in both male and female birds, and the immunophysiology of birds. The Sixth Edition, like the earlier editions, is a must for anyone interested in comparative physiology, poultry science, veterinary medicine, and related fields. This volume establishes the standard for those who need the latest and best information on the physiology of birds. Includes new chapters on endocrine disruptors, magnetoreception, genomics, proteomics, mitochondria, control of food intake, molting, stress, the avian endocrine system, bone, the metabolic demands of migration, behavior and control of body temperature Features extensively revised chapters on the cardiovascular system, pancreatic hormones, respiration, pineal gland, pituitary gland, thyroid, adrenal gland, muscle, gastro-intestinal physiology, incubation, circadian rhythms, annual cycles, flight, the avian immune system, embryo physiology and control of calcium Stands out as the only comprehensive, single volume devoted to bird physiology Offers a full consideration of both blood and avian metabolism on the companion website (http://booksite.elsevier.com/ 9780124071605). Tables feature hematological and serum biochemical parameters together with circulating concentrations of glucose in more than 200 different species of wild birds
Update On Emerging Treatments For Migraine
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Author :
language : en
Publisher: Elsevier
Release Date : 2020-09-05
Update On Emerging Treatments For Migraine written by and has been published by Elsevier this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-09-05 with Science categories.
Update on Emerging Treatments for Migraine, Volume 255, the latest release in the Progress in Brain Research 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 Progress in Brain Research series Updated release includes the latest information on Update on Emerging Treatments for Migraine