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Book
From Peptide and Protein Toxins to Ion Channel Structure/Function and Drug Design
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Year: 2020 Publisher: Frontiers Media SA

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact


Dissertation
Biochemische karakterisatie van een prokaryote homoloog van het humaan ether-à-go-go related gene kanaal
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Year: 2012 Publisher: Leuven KU Leuven. Faculteit Farmaceutische Wetenschappen

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Dissertation
Nieuwe behandelingsstrategieën voor insomnia
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Year: 2013 Publisher: Leuven KUL

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Dissertation
Structurele en functionele karakterisatie van en prokaryoot pLGIC
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Year: 2014 Publisher: Leuven KUL

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Dissertation
Mutagenese, expressie en kristallisatie van een 5HT3-receptor homoloog & in silico alignement van ACHBP met de glycine receptor en aanmaak van een glycine receptor homoloog
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Year: 2009 Publisher: Leuven KU Leuven. Faculteit Farmaceutische Wetenschappen

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Book
From Peptide and Protein Toxins to Ion Channel Structure/Function and Drug Design
Authors: --- --- ---
Year: 2020 Publisher: Frontiers Media SA

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Abstract

This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact


Dissertation
Opioid receptor signaling : from drug to effector. A focus on GIRK and HCN channels.

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Book
From Peptide and Protein Toxins to Ion Channel Structure/Function and Drug Design
Authors: --- --- ---
Year: 2020 Publisher: Frontiers Media SA

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Abstract

This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact


Dissertation
X-ray structure of a humanized acetylcholine-binding protein as a template for fragment-based drug discovery
Authors: --- ---
Year: 2017 Publisher: Leuven KU Leuven. Faculteit Geneeskunde

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The α7 nicotinic acetylcholine receptor (nAChR) is an excitatory ligand-gated ion channel activated by the neurotransmitter acetylcholine. Dysfunction of the cholinergic system has been shown to be involved in Alzheimer’s disease and schizophrenia. Both conditions are characterized by decreased α7 nAChR expression in key brain areas involved in cognition, including the hippocampus and cortex. A potential novel therapeutic strategy to improve cognition is positive-allosteric modulation of the α7 nAChR. This implies that a positive-allosteric modulator (PAM) binds to a different site of the receptor than acetylcholine, thereby enhancing α7 nAChR function when acetylcholine is present. The PAM will be developed by structure-based drug design. However, the structure of the human α7 nAChR at atomic resolution is currently unavailable. Therefore, a humanized chimaeric receptor composed of human α7 nAChR and Lymnaea stagnalis acetylcholine-binding protein sequences (α7 AChBP) was used as a surrogate for the extracellular domain of the human α7 nAChR. In order to improve the model, sharing 71 % sequence similarity with the human α7 nAChR, seven additional humanizing mutations were introduced in the vestibule pocket. This pocket corresponds to a site involved in positive-allosteric modulation of ELIC by benzodiazepines. Previously, several allosteric modulators binding in the vestibule pocket of α7 AChBP, have been identified. In this study, the X-ray structure of α7 AChBP, with seven additional humanizing mutations in the vestibule pocket, was determined. Afterwards, fragment library screening at the XChem fragment screening facility of the Diamond was performed and the structure was solved in presence of different fragments.

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Dissertation
Prekristallisatie screening op basis van stabiliteit van Cys-loop receptor homologen
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Year: 2016 Publisher: Leuven KU Leuven. Faculteit Farmaceutische Wetenschappen

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Cys-loop receptoren of pentamere ligand-geactiveerde ionenkanalen zijn verantwoordelijk voor snelle exciterende en inhiberende neurotransmissie in het perifere en centrale zenuwstelsel. Dysfunctie van deze receptoren speelt een belangrijke rol in verscheidene neurologische aandoeningen en bovendien vormen pLGICs een belangrijk klinisch doelwit voor een aantal frequent voorgeschreven geneesmiddelen. Een betere kennis van structuur, neurotransmitter modulatie en ligand herkenning zou leiden tot verbeterde pathofysiologische inzichten en zou een rationele structuur-gebaseerde geneesmiddelenontwikkeling ondersteunen. Structurele en functionele studies openen dus deuren naar selectievere en effectievere geneesmiddelen of behandelingen. Deze studie is gericht op het karakteriseren van de thermische stabiliteit van een invertebrate Cys-loop receptor homoloog genaamd Alpo 4 uit Alvinella pompejana. Alpo 4 is een kation-selectief kanaal. Het deelt een 25,89% sequentie identiteit met de humane 7 nicotine acetylcholine receptor en 24,67% sequentie identiteit met de 5-HT3A receptor. Additie van steroïde-afgeleide detergenten CHAPS en CHAPSO leidde tot een verhoogde thermische stabiliteit van Alpo 4 eGFP ic. Uitgaande van dit experiment werd Alpo 4 wild type opgezuiverd met CHAPS als additief, wat leidde tot een succesvolle opzuivering met verhoogde opbrengst en goed gelfiltratieprofiel. Met het opgezuiverd eiwit werden kristallisatiepogingen gedaan.

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