Combinational and Evolutionary Approaches of the Investigation of Receptor-ligand Interactions PDF Download
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Author: Bernhard Michael Schimmele
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Author: Bernhard Michael Schimmele
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Author: Bernhard Michael Schimmele
Publisher:
ISBN:
Category :
Languages : en
Pages : 209
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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: Adam Moore
Publisher:
ISBN:
Category :
Languages : en
Pages :
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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: Matthew Joseph Styles
Publisher:
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Category :
Languages : en
Pages :
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Many common Gram-negative bacteria, including important human pathogens, utilize small molecule signals (N-acyl-L-homoserine lactones, or AHLs) and cognate receptors (LuxR-type receptors) to control group phenotypes, such as virulence factor production, using a cell-to-cell signaling process called quorum sensing (QS). AHLs bind to LuxR-type receptors at high cell densities, which activates a series of macromolecular interactions that lead to altered expression of QS-regulated genes. QS has attracted significant recent attention as a target to block infections in humans, and numerous chemical biology approaches have been aimed towards disrupting this communication process in order to attenuate bacterial virulence. Small molecules that selectively target LuxR-type receptors represent one such approach. To develop these chemical tools, we must significantly expand our understanding of LuxR-type receptor:ligand interactions. These receptors have proven challenging targets for biophysical investigation, especially in the presence of compounds that antagonize receptor activity. This thesis focuses on the development of methods for characterizing LuxR-type receptor:ligand interactions using a combination of chemical biology, biochemical, and biophysical approaches.We began by identifying and developing structure-activity relationships for chemical probes capable of agonizing and antagonizing the orphan LuxR-type QS receptor SdiA in Salmonella and E. coli, characterizing the mechanism of action for a covalent inhibitor, and demonstrating the ability of this inhibitor to interfere with an infection-related phenotype (acid resistance). We next developed a FoÌ8rster Resonance Energy Transfer (FRET) assay to monitor LuxR-type receptor ligand binding in vitro and in intact cells and demonstrated the compatibility of these assays with six LuxR-type receptors. Thereafter, we report a series of biophysical experiments to characterize the interactions of two LuxR-type receptors, QscR from P. aeruginosa and SdiA form E. coli, with a range of small molecules agonists and antagonists. Based on these results, we propose models for the underlying signal transduction mechanism for each receptor. Critically, these results suggest several limitations of standard cell-based reporter assays as proxies for different biophysical parameters, and we provide an alternate path for mechanistic investigations that avoid these limitations. The results presented here provide chemical tools, methods, and conceptual models that will advance chemical approaches to modulate QS.
Author: Yury E. Khudyakov
Publisher: CRC Press
ISBN: 1420007300
Category : Medical
Languages : en
Pages : 588
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Book Description
An All-Inclusive Review of the Achievements and Trends in the Fast-Growing Protein Engineering Field From humble beginnings like making fire for mere survival, engineering now steadfastly penetrates all aspects of our lives and even life itself at the molecular level. Protein engineering is a molecular biological discipline focused on designing and
Author: Dastmalchi, Siavoush
Publisher: IGI Global
ISBN: 1522503633
Category : Medical
Languages : en
Pages : 386
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Book Description
As the pharmaceutical industry continues to advance, new techniques in drug design are emerging. In order to deliver optimum care to patients, the development of innovative pharmacological techniques has become a widely studied topic. Applied Case Studies and Solutions in Molecular Docking-Based Drug Design is a pivotal reference source for the latest scholarly research on the progress of pharmaceutical design and computational approaches in the field of molecular docking. Highlighting innovative research perspectives and real-world applications, this book is ideally designed for professionals, researchers, practitioners, and medical chemists actively involved in computational chemistry and pharmaceutical sciences.
Author: Wafik S. El-Deiry
Publisher: Springer Science & Business Media
ISBN: 1588291723
Category : Medical
Languages : en
Pages : 374
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Book Description
An in depth review of our latest understanding of the molecular events that regulate cell death and those molecules that provide targets for developing agonists or antagonists to modulate death signaling for therapeutic purposes. The authors focus on the extrinsic system of death receptors, their regulation and function, and their abnormalities in cancer. Topics of particular interest include resistance to apoptosis, TRAIL signaling, death receptors in embryonic development, mechanisms of caspase activation, and death receptor mutations in cancer. Additional chapters address death signaling in melanoma, synthetic retinoids and death receptors, the role of p53 in death receptor regulation, immune suppression of cancer, and combination therapy with death ligands.
Author:
Publisher:
ISBN:
Category : Medicine
Languages : en
Pages : 2160
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Book Description
Vols. for 1963- include as pt. 2 of the Jan. issue: Medical subject headings.
