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Author: Hulme
Publisher:
ISBN: 9781852211004
Category :
Languages : en
Pages :
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Author: Hans-Joachim Böhm
Publisher: John Wiley & Sons
ISBN: 3527605517
Category : Science
Languages : de
Pages : 262
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Book Description
The lock-and-key principle formulated by Emil Fischer as early as the end of the 19th century has still not lost any of its significance for the life sciences. The basic aspects of ligand-protein interaction may be summarized under the term 'molecular recognition' and concern the specificity as well as stability of ligand binding. Molecular recognition is thus a central topic in the development of active substances, since stability and specificity determine whether a substance can be used as a drug. Nowadays, computer-aided prediction and intelligent molecular design make a large contribution to the constant search for, e. g., improved enzyme inhibitors, and new concepts such as that of pharmacophores are being developed. An up-to-date presentation of an eternally young topic, this book is an indispensable information source for chemists, biochemists and pharmacologists dealing with the binding of ligands to proteins.
Author: Hulme
Publisher:
ISBN: 9781852211004
Category :
Languages : en
Pages :
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Author: E. C. Hulme
Publisher: Oxford University Press, USA
ISBN:
Category : Medical
Languages : en
Pages : 486
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Book Description
This is the final volume in a set of 3 books detailing practical methods for the investigation of biochemical receptors. This book deals with the performance and interpretation of receptor-ligand binding studies which are important in many areas of pharmacological and neurochemical research.
Author: Holger Gohlke
Publisher: John Wiley & Sons
ISBN: 3527329668
Category : Medical
Languages : en
Pages : 361
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Book Description
Innovative and forward-looking, this volume focuses on recent achievements in this rapidly progressing field and looks at future potential for development. The first part provides a basic understanding of the factors governing protein-ligand interactions, followed by a comparison of key experimental methods (calorimetry, surface plasmon resonance, NMR) used in generating interaction data. The second half of the book is devoted to insilico methods of modeling and predicting molecular recognition and binding, ranging from first principles-based to approximate ones. Here, as elsewhere in the book, emphasis is placed on novel approaches and recent improvements to established methods. The final part looks at unresolved challenges, and the strategies to address them. With the content relevant for all drug classes and therapeutic fields, this is an inspiring and often-consulted guide to the complexity of protein-ligand interaction modeling and analysis for both novices and experts.
Author: Flavio Ballante
Publisher:
ISBN: 9781071612095
Category : Cheminformatics
Languages : en
Pages : 327
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Book Description
This detailed book collects modern and established computer-based methods aimed at addressing the drug discovery challenge from disparate perspectives by exploiting information on ligand-protein recognition. Beginning with methods that allow for the exploration of specific areas of chemical space and the designing of virtual libraries, the volume continues with sections on methods based on docking, quantitative models, and molecular dynamics simulations, which are employed for ligand discovery or development, as well as methods exploiting an ensemble of protein structures for the identification of potential protein targets. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Protein-Ligand Interactions and Drug Design provides detailed practical procedures of solid computer-aided drug design methodologies employed to rationalize and optimize protein-ligand interactions, for experienced researchers and novices alike.
Author: James Kenneth Chen
Publisher:
ISBN:
Category : Receptor-ligand complexes
Languages : en
Pages : 444
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Book Description
Author: Ulrike Koehl
Publisher: Frontiers Media SA
ISBN: 2889456633
Category : Immunologic diseases. Allergy
Languages : en
Pages : 407
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Book Description
Recognition and killing of aberrant, infected or tumor targets by Natural Killer (NK) cells is mediated by positive signals transduced by activating receptors upon engagement of ligands on target surface. These stimulatory pathways are counterbalanced by inhibitory receptors that raise NK cell activation threshold through negative antagonist signals. While regulatory effects are necessary for physiologic control of autoimmune aggression, they may restrain the ability of NK cells to activate against disease. Overcoming this barrier to immune surveillance, multiple approaches to enhance NK-mediated responses are being investigated since two decades. Propelled by considerable advances in the understanding of NK cell biology, these studies are critical for effective translation of NK-based immunotherapy principles into the clinic. In humans, dominant inhibitory signals are transduced by Killer Immunoglobulin Like Receptors (KIR) recognizing cognate HLA class I on target cells. Conversely, KIR recognition of “missing self-HLA” - due to HLA loss or HLA/ KIR mismatch - triggers NK-mediated tumor rejection. Initially observed in murine transplant models, these antitumor effects were later found to have important implications for the clinical outcome of haplotype-mismatched stemcell transplantation. Here, donor NK subsets protect against acute myeloid leukemia (AML) relapse through missing self recognition of donor HLA-C allele groups (C1 or C2) and/or Bw4 epitope. These studies were subsequently extended by trials investigating the antileukemia effects of adoptively transferred haplotype-mismatched NK cells in non-transplant settings. Other mechanisms have been found to induce clinically relevant NK cell alloreactivity in transplantation, e.g., post-reconstitution functional reversal of anergic NK cells. More recently, activating KIR came into the spotlight for their potential ability to directly activate donor NK cells through in vivo recognition of HLA or other ligands. Novel therapeutic monoclonal antibodies (mAb) may optimize NK-mediated effects. Examples include obinutuzumab (GA101), a glyco-engineered anti-CD20 mAb with increased affinity for the FcγRIIIA receptor, enhancing antibody-dependent cellular cytotoxicity; lirilumab (IPH2102), a first-in-class NK-specific checkpoint inhibitor, blocking the interaction between the major KIR and cognate HLA-C antigens; and elotuzumab (HuLuc63), a humanized monoclonal antibody specific for SLAMF7, whose anti-myeloma therapeutic effects are partly due to direct activation of SLAMF7-expressing NK cells. In addition to conventional antibodies, NK cell-targeted bispecific (BiKEs) and trispecific (TriKEs) killer engagers have also been developed. These proteins elicit potent effector functions by binding target ligands (e.g., CD19, CD22, CD30, CD133, HLA class II, EGFR) on one arm and NK receptors on the other. An additional innovative approach to direct NK cell activity is genetic reprogramming with chimeric antigen receptors (CAR). To date, primary NK cells and the NK92 cell line have been engineered with CAR specific for antigens expressed on multiple tumors. Encouraging preclinical results warrant further development of this approach. This Research Topic welcomes contributions addressing mechanisms of NK-mediated activation in response to disease as well as past and contemporary strategies to enhance NK mediated reactivity through control of the interactions between NK receptors and their ligands.
Author: Mark A. Williams
Publisher: Humana
ISBN: 9781493958733
Category : Science
Languages : en
Pages : 0
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Book Description
Proteins are the cell’s workers, their messengers and overseers. In these roles, proteins specifically bind small molecules, nucleic acid and other protein partners. Cellular systems are closely regulated and biologically significant changes in populations of particular protein complexes correspond to very small variations of their thermodynamics or kinetics of reaction. Interfering with the interactions of proteins is the dominant strategy in the development of new pharmaceuticals. Protein Ligand Interactions: Methods and Applications, Second Edition provides a complete introduction to common and emerging procedures for characterizing the interactions of individual proteins. From the initial discovery of natural substrates or potential drug leads, to the detailed quantitative understanding of the mechanism of interaction, all stages of the research process are covered with a focus on those techniques that are, or are anticipated to become, widely accessible and performable with mainstream commercial instrumentation. Written in the highly successful Methods in Molecular Biology series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Protein Ligand Interactions: Methods and Applications, Second Edition serves as an ideal guide for researchers new to the field of biophysical characterization of protein interactions – whether they are beginning graduate students or experts in allied areas of molecular cell biology, microbiology, pharmacology, medicinal chemistry or structural biology.
Author: Anthony P. Davenport
Publisher: Humana Press
ISBN: 9781617799082
Category : Science
Languages : en
Pages : 0
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Book Description
A broad definition of a receptor is a specialized protein on or in a cell that recognizes and binds a specific ligand to undergo a conformational change, leading to a physiological response or change in cell function. A ligand can be an endogenous neurotransmitter, hormone, paracrine/autocrine factor, or a synthetic drug that may function as an agonist or antagonist. The third edition of Receptor Binding Techniques expands upon the methods and techniques used for studying receptors in silico, in vitro and in vivo. Comprehensive chapters describe how to use online resources for experimental research such as prediction of receptor-ligand interactions and mine the IUPHAR receptor database. Classical techniques of radioligand binding, quantitative autoradiography and their analyses are complemented by the use of immunocytochemistry for the cellular localization of receptor protein and hybridization to detect receptor mRNA. Protocols using fluorescent labeled ligands are described to visualise receptors in living cells, their interaction with beta-arrestin to measure ligand-induced internalisation and green fluorescent protein to study trafficking. Non-radioactive, chemiluminescent cAMP and arrestin assays facilitate the identification of novel ‘biased agonists’. Detailed methods are provided for in vivo imaging of receptors using positron emission tomography (PET). Written in the highly successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Receptor Binding Techniques, Third Edition, aids scientists in continuing to study receptor binding.
Author: Bernhard Michael Schimmele
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
