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Aptamer gpcr

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https://www.readbyqxmd.com/read/29735399/emerging-paradigm-of-intracellular-targeting-of-g-protein-coupled-receptors
#1
REVIEW
Madhu Chaturvedi, Justin Schilling, Alexandre Beautrait, Michel Bouvier, Jeffrey L Benovic, Arun K Shukla
G protein-coupled receptors (GPCRs) recognize a diverse array of extracellular stimuli, and they mediate a broad repertoire of signaling events involved in human physiology. Although the major effort on targeting GPCRs has typically been focused on their extracellular surface, a series of recent developments now unfold the possibility of targeting them from the intracellular side as well. Allosteric modulators binding to the cytoplasmic surface of GPCRs have now been described, and their structural mechanisms are elucidated by high-resolution crystal structures...
July 2018: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/29538413/functional-autoantibodies-in-patients-with-different-forms-of-dementia
#2
Gerd Wallukat, Harald Prüss, Johannes Müller, Ingolf Schimke
Dementia in general and Alzheimer's disease in particular is increasingly seen in association with autoimmunity being causatively or supportively involved in the pathogenesis. Besides classic autoantibodies (AABs) present in dementia patients, there is the new autoantibody class called functional autoantibodies, which is directed against G-protein coupled receptors (GPCRs; GPCR-AABs) and are seen as pathogenic players. However, less is known about dementia patients' burden with functional autoantibodies. We present here for the first time a study analyzing the prevalence of GPCR-AABs in patients with different dementia forms such as unclassified, Lewy body, vascular and Alzheimer's dementia...
2018: PloS One
https://www.readbyqxmd.com/read/27398998/conformationally-selective-rna-aptamers-allosterically-modulate-the-%C3%AE-2-adrenoceptor
#3
Alem W Kahsai, James W Wisler, Jungmin Lee, Seungkirl Ahn, Thomas J Cahill Iii, S Moses Dennison, Dean P Staus, Alex R B Thomsen, Kara M Anasti, Biswaranjan Pani, Laura M Wingler, Hemant Desai, Kristin M Bompiani, Ryan T Strachan, Xiaoxia Qin, S Munir Alam, Bruce A Sullenger, Robert J Lefkowitz
G-protein-coupled receptor (GPCR) ligands function by stabilizing multiple, functionally distinct receptor conformations. This property underlies the ability of 'biased agonists' to activate specific subsets of a given receptor's signaling profile. However, stabilizing distinct active GPCR conformations to enable structural characterization of mechanisms underlying GPCR activation remains difficult. These challenges have accentuated the need for receptor tools that allosterically stabilize and regulate receptor function through unique, previously unappreciated mechanisms...
September 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/26584137/aptamer-bc007-for-neutralization-of-pathogenic-autoantibodies-directed-against-g-protein-coupled-receptors-a-vision-of-future-treatment-of-patients-with-cardiomyopathies-and-positivity-for-those-autoantibodies
#4
Gerd Wallukat, Johannes Müller, Annekathrin Haberland, Sabine Berg, Angela Schulz, Ernst-Joachim Freyse, Roland Vetter, Eckhard Salzsieder, Reinhold Kreutz, Ingolf Schimke
Cardiomyopathies such as idiopathic dilated cardiomyopathy (DCM), Chagas' cardiomyopathy and Peripartum cardiomyopathy present with autoantibodies against G-protein coupled receptors (GPCR-AABs) that agonistically activate their receptors. For the treatment of "agonistic autoantibody diseases" and in particular DCM, the removal of the GPCR-AABs by immunoadsorption (IA) has been studied with convincing patient benefit. To overcome cost and logistics problems of IA, the application of the aptamer BC007 for in vivo neutralization of GPCR-AABs could help...
January 2016: Atherosclerosis
https://www.readbyqxmd.com/read/24777744/agonistic-autoantibodies-directed-against-g-protein-coupled-receptors-and-their-relationship-to-cardiovascular-diseases
#5
REVIEW
Gerd Wallukat, Ingolf Schimke
Agonistic autoantibodies (AABs) against G-protein-coupled receptor (GPCR) are present mainly in diseases of the cardiovascular system or in diseases associated with cardiovascular disturbances. The increasing knowledge about the role of autoantibodies against G-protein-coupled receptor (GPCR-AABs) as pathogenic drivers, the resulting development of strategies aimed at their removal or neutralization, and the evidenced patient benefit associated with such therapies have created the need for a summary of GPCR-AAB-associated diseases...
May 2014: Seminars in Immunopathology
https://www.readbyqxmd.com/read/12054450/generation-of-rna-aptamers-to-the-g-protein-coupled-receptor-for-neurotensin-nts-1
#6
Dion A Daniels, Awinder K Sohal, Stephen Rees, Reinhard Grisshammer
G-protein-coupled receptors (GPCRs) are integral membrane proteins involved in signal transduction and constitute major drug targets for disease therapy. Aptamers, which are globular RNA or DNA molecules evolved to specifically bind a target, could represent a valuable tool with which to probe the role of such receptors in normal tissue and disease pathology and for cocrystallization with receptors for structure determination by X-ray crystallography. Using the bacterially expressed rat neurotensin receptor NTS-1 as an example, we describe a strategy for the generation of GPCR-specific RNA aptamers...
June 15, 2002: Analytical Biochemistry
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