The Melanocortin Receptors

The Melanocortin Receptors

The book illuminates the structure and function of these receptors through a wide-ranging review of the latest findings concerning the biology, physiology, and pharmacology of their peptide ligands and covers the major melanocortin ...

Author: Roger D. Cone

Publisher: Springer Science & Business Media

ISBN: 9781592590315

Category: Medical

Page: 542

View: 344

Roger Cone and a distinguished team of expert investigators provide the first major treatment of this critically important receptor family. The book illuminates the structure and function of these receptors through a wide-ranging review of the latest findings concerning the biology, physiology, and pharmacology of their peptide ligands and covers the major melanocortin peptides, Melanocortin-1-Receptors through Melanocortin-5-Receptors. Topics include the characterization of the melanocortin receptors, the biochemical mechanism of receptor action, and receptor function and regulation. Timely and authoritative, The Melanocortin Receptors offers an up-to-date knowledge base on the remarkably complex structure and functions of the melanocortins, a guide that will prove invaluable for today's neuroscientists, endocrinologists, pharmacologists, and other clinical and experimental investigators working in this fast moving field.
Categories: Medical

Corticotropin Receptors Advances in Research and Application 2012 Edition

Corticotropin Receptors   Advances in Research and Application  2012 Edition

Corticotropin Receptors—Advances in Research and Application: 2012 Edition is a ScholarlyPaper™ that delivers timely, authoritative, and intensively focused information about Corticotropin Receptors in a compact format.

Author:

Publisher: ScholarlyEditions

ISBN: 9781481634007

Category: Medical

Page: 21

View: 589

Corticotropin Receptors—Advances in Research and Application: 2012 Edition is a ScholarlyPaper™ that delivers timely, authoritative, and intensively focused information about Corticotropin Receptors in a compact format. The editors have built Corticotropin Receptors—Advances in Research and Application: 2012 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Corticotropin Receptors in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Corticotropin Receptors—Advances in Research and Application: 2012 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.
Categories: Medical

Melanocortins

Melanocortins

The evidence to support academic interest and clinical applications lies in significant part within the chapters of this book, chapters written by noted experts in the field who have worked diligently to understand the molecules and to move ...

Author: Anna Catania

Publisher: Springer Science & Business Media

ISBN: 9781441963543

Category: Medical

Page: 153

View: 599

It is clear that the melanocortins are of immense academic interest. Further, these molecules have remarkable potential as pharmaceutical agents for treatment of multiple human and veterinary disorders and diseases. The evidence to support academic interest and clinical applications lies in significant part within the chapters of this book, chapters written by noted experts in the field who have worked diligently to understand the molecules and to move them toward clinical applications. I personally believe that the - MSH molecule and its derivatives will be used as routine therapeutics in the very near future. My belief is so strong that I left academia to form a company based on -MSH analogs and have caused millions of dollars to be spent on melanocortin research. Now why would a sane professor pick up such a challenge and enter business, an essential step toward any clinical application? It is the - MSH story that drove me. Consider that - MSH occurs in exactly the same amino acid sequence in humans and in the sea lamprey, an organism unchanged since its appearance during the Pennsylvanian period of the Paleozoic era (about 300 million years ago—way before dinosaurs were to be considered). There is unpublished evidence that the stability of the molecule can be traced back a half billion years. Frankly, I believe that the molecule existed even when single cells began to live together.
Categories: Medical

The Melanocortin System Structure Activity Relationships of Alpha N Methylated MT II Analogues and Mutation Studies of Human Melanocortin Receptor Subtypes 1 and 4

The Melanocortin System  Structure Activity Relationships of Alpha N Methylated MT II Analogues and Mutation Studies of Human Melanocortin Receptor Subtypes 1 and 4

The melanocortin system regulates various physiological processes including feeding behavior, sexual function, skin pigmentation and photoprotection via five G-protein coupled receptors and several endogenous ligands.

Author:

Publisher:

ISBN: OCLC:659748470

Category:

Page: 178

View: 396

The melanocortin system regulates various physiological processes including feeding behavior, sexual function, skin pigmentation and photoprotection via five G-protein coupled receptors and several endogenous ligands. There is a need for selective and potent ligands to the human melanocortin receptors (hMCRs) that can chemically resolve these various functions. This thesis presents three studies aimed at refining the understanding of the structural differences between binding pockets of the hMCR subtypes. In the first study0ł-N-methylated analogues of the non-selective agonist, MT-II, are evaluated for their in vitro function. This study produced the most potent hMC1R selective agonist to date. The following two studies examine the effects of mutations on the biological activity of melanocortin receptor subtypes 1 and 4. Much of the mutation study data is preliminary and requires a demonstration of reproducibility.
Categories:

Developing Melanocortin 3 Selective Ligands Through C Terminal Modification of Melanocortin Peptides

Developing Melanocortin 3 Selective Ligands Through C Terminal Modification of Melanocortin Peptides

The melanocortin 3 and 4 receptors share 58% overall amino acid identity and 76% similarity.

Author: Joel Benjamin Nyberg

Publisher:

ISBN: OCLC:841561273

Category:

Page: 568

View: 175

The melanocortin 3 and 4 receptors share 58% overall amino acid identity and 76% similarity. This high level of similarity between the MC3R and the MC4R underscores the difficulties associated with developing MC3R selective ligands, and as a consequence little is known of the physiological functions of the melanocortin 3 receptor. Previous research showing the differences between endogenous non-selective ligands and melanocortin 3 receptor selective ligands are mainly within the C-terminus of the melanocortin peptide. These findings have been exploited in this research using known melanocortin 3 and 4 selective ligands modified at their respective C-termini to develop some very promising melancortin 3 selective antagonists and agonists, analog 5 ([CO(CH2)2CO-DNal(2')-Arg-Trp-Lys]-Gly-Lys-Pro-Val-NH2) and analog 20 ((H-DNal(2')-c[Asp-Pr6-DPhe-Arg-Trp-Lys]-Ala-Gly-Pro-Val-NH2) respectively. Additional studies using molecular modeling have produced further insights into the structural basis for selectivity. Finally, we have been developing a new scaffold for the melanocortin receptor using cyclic dipeptide derivatives.
Categories:

NMR Studies of Structure and Dynamics of Novel Peptide based Melanocortin Receptor Antagonists

NMR Studies of Structure and Dynamics of Novel Peptide based Melanocortin Receptor Antagonists

ABSTRACT: Obesity has become one of the leading diseases in the developed countries, leading to other health-related problems like heart disease and diabetes.

Author: Ramanan Thirumoorthy

Publisher:

ISBN: OCLC:51748489

Category: Nuclear magnetic resonance

Page:

View: 163

ABSTRACT: Obesity has become one of the leading diseases in the developed countries, leading to other health-related problems like heart disease and diabetes. Melanocortin receptors (MCRs) are G-protein coupled receptors that are expressed in a variety of tissues, including the skin and the brain. There is evidence suggesting that brain MCRs, for which the agouti-related protein (AGRP) is an antagonist, modulate feeding behavior. In this study, peptides based on the AGRP(109-118) decapeptide, Tyr-c[Cys-Arg-Phe-Phe-Asn-Ala-Phe-Cys]-Tyr-NH2, were designed and synthesized by replacing the 26-membered disulfide Cys2-Cys9 ring with lactam bridges to provide varying sizes of the ring by substituting with different bridging residues. The three cyclic peptides designed differ in ring chain length by one carbon atom. Of the three peptides, Tyr-c[Glu-Arg-Phe-Phe-Asn-Ala-Phe-Dpr]-Tyr-NH2 was found to be a novel antagonist of the type-1 MCR (MC1R) present in skin, while the other two peptides were found to be agonists. It was interesting to find that, although the peptides vary by only one carbon atom, they were found to have different biological properties. An extensive set of NMR measurements and molecular modeling studies was carried out to delineate the structural features that mediate the biological properties of these compounds at the MC1R and MC4R. To further understand the dynamics of the peptides, NMR relaxation parameters were recorded and analyzed. The structure and dynamics of the peptides also were found to be significantly different. Details of the studies are reported in this dissertation.
Categories: Nuclear magnetic resonance

G Protein Coupled Receptors in Energy Homeostasis and Obesity Pathogenesis

G Protein Coupled Receptors in Energy Homeostasis and Obesity Pathogenesis

Reviews in this volume of Progress in Molecular Biology and Translational Science summarize current status in studies of a number of G protein-coupled receptors that were shown to be promising targets for obesity treatments.

Author:

Publisher: Academic Press

ISBN: 9780123869524

Category: Science

Page: 400

View: 316

Obesity is an epidemic with enormous health, economic and social burdens. Current drugs for obesity treatment are far from ideal in terms of efficacy and side effects. Reviews in this volume of Progress in Molecular Biology and Translational Science summarize current status in studies of a number of G protein-coupled receptors that were shown to be promising targets for obesity treatments. Some of these receptors also cause monogenic obesity in humans. Subject matter: obesity is an epidemic and G protein-coupled receptors are promising drug targets, with significant potential as new anti-obesity drugs Chapters are written by leading experts
Categories: Science