71 zoekresultaten voor “enzyme” in de Publieke website
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Chemical genetic approaches for target validation
Drug development is a time- and resource-consuming process that starts with the discovery and validation of a (protein) target that contributes to pathogenesis or disease progression.
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Photocleavable activity-based acid glucosylceramidase probes
Lysosomal acid glucosylceramidase (GBA1) is a lysosomal enzyme that degrades glucolipids with its main substrate being glucosylceramide (GlcCer). Defects in the GBA1 gene lead to glycosphingolipidosis Gaucher disease (GD), in which the hydrolysis of GlcCer is impaired and therefore, it accumulates in…
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Antibiotic Discovery: From mechanistic studies to target ID
The investigations described in this thesis lay out strategies aimed at advancing antibiotic research and development. The examples presented revolve around two main approaches: understanding drug-target interactions and target identification.
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Applications for activity-based probes in biomedical research on glycosidases
Lysosomal glycosidases are acid hydrolases that fragment glycoconjugates in lysosomes.
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Inhibitors and activity-based probes for β-D-glucuronidases, heparanases and β-L-arabinofuranosidases
Glycosidases (GHs) are enzymes responsible for the degradation of carbohydrates and play many roles in human health and pathophysiology. Often, abnormal levels of glycosidase activity are markedly linked to human pathologies.
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Chemical tools to study lipid signaling
Synthesis and application of chemical biology tools to study immunomodulatory signaling lipids.
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Systems pharmacology of the amyloid cascade
According to the amyloid cascade hypothesis, accumulation of beta-amyloid (Aβ) peptides initiates the pathological cascade in Alzheimer's disease (AD).
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Morphogenesis and heterogeneity in liquid-grown streptomyces cultures
The filamentous bacteria Streptomyces are widespread inhabitants of terrestrial soils.
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Design and development of conformational inhibitors and activity-based probes for retaining glycosidases
Glycosidases are essential in fundamental biological processes and are responsible for the degradation of most (oligo)saccharides, glycolipids and glycoproteins.
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Structural characterization of bacterial proteins involved in antibiotic resistance and peptidoglycan biosynthesis
This thesis describes the structural and biochemical characterization of the β-lactamase BlaC from Mycobacterium tuberculosis (Mtb), and the Alr and YlmE proteins from Streptomyces coelicolor A3(2).Mtb is the main cause of tuberculosis.
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Inhibitors and probes targeting mannanases
This thesis describes the synthesis and biochemical evaluation of a variety of cyclophellitol based activity-based probes and inhibitors targeting various endo- and exo-acting retaining glycosidases. In the last two decades a variety of probes and inhibitors for (hemi)cellulose degrading enzymes have…
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The electrochemical reduction of dioxygen and hydrogen peroxide by molecular copper catalysts
The electrochemical oxygen reduction reaction (ORR) is an essential half-reaction for the utilization of hydrogen as a sustainable fuel, via the conversion of hydrogen to electrons and protons facilitated by the ORR. In the most common fuel cells, the ORR is requires high loadings of non-abundant platinum…
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CD8+ T-cells in atherosclerosis: mechanistic studies revealing a protective role in the plaque microenvironment
Atherosclerosis is the most important underlying process that drives cardiovascular disease, and is characterized by an accumulation of cholesterol which triggers an inflammatory response in the vessel wall.
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Systems pharmacology of the endocannabinoid system
In this thesis, a system pharmacology approach, integrating metabolomics, pharmacology and chemical biology, was applied to understand and modulate the endocannabinoid system across different model systems (cells, zebrafish, mice and humans).
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Cyclophellitol analogues for profiling of exo- and endo-glycosidases
To this day, all cyclophellitol-based inhibitors and ABPs have been close analogues of their natural substrate counterparts. As a result, these probes showed high selectivity towards their target glycosidases.
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Synthetic Methodology Towards ADP-Ribosylation Related Molecular Tools
Phosphorylation affects all four major biomolecules – proteins, lipids, carbohydrates and nucleic acids – and plays a pivotal role in the most fundamental cellular functions.
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Negentien Veni subsidies voor Leiden, zeven voor Wiskunde en Natuurwetenschappen
Negentien Leidse recent gepromoveerde onderzoekers kregen deze herfst een Veni-subsidie van NWO toegekend, zeven daarvan zijn voor onze faculteit. Elke onderzoeker krijgt 250.000 euro voor drie jaar onderzoek. Landelijk werden161 projecten gehonoreerd.
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Zenith subsidie voor Hermen Overkleeft
Hermen Overkleeft ontving samen met Bobby Florea een Zenith subsidie van het Horizon-programma van het Nederland Genomics Initiative voor hun voorstel Quantative functional enzyme profiling: a versatile strategy to monitor disease progression and to validate new therapeutic strategies'.
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Doorbraak Leidse wetenschappers in bestuderen ziekte van Pompe
Wetenschappers van de Universiteit Leiden hebben een doorbraak bereikt in de bestudering van de erfelijke stofwisselingsziekte van Pompe. Samen met hun Yorkse collega’s ontwierpen zij een molecuul dat zich bindt aan het enzym dat aan de basis staat van het ziekteverloop. De bevindingen zijn gepubliceerd…
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Exploring Ubiquitin and ISG15 Biology with Chemical Tools
Promotie
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Samenwerken voor efficiënte medicijnontwikkeling
De keten die patiënten voorziet van nieuwe medicijnen, bestaat uit diverse complexe schakels: van fundamentele wetenschap, tot klinische tests, tot productie. Deze hele keten is aanwezig in Leiden. De Universiteit Leiden, het Leids Universitair Medisch Centrum (LUMC) en de bedrijven op het Leiden Bio…