Promotor: G.A. van der Marel, Co-promotor: J.D.C. Codée

Lysosomal storage disorders (LSDs) are a group of orphan diseases characterized by lysosomal dysfunction or impaired lysosomal catabolism and affect collectively about 1 in 5000 live births.

In this thesis an activity-based probe was discovered that could visualize the activity of PLAATs. With an optimized gel-based ABPP assay in hand, screening of a compound library led to the discovery of alpha-ketoamides as a hit for PLAAT3.

In surface science there is great effort to move from studying simple, flat model surfaces in vacuum to investigating more complex model catalysts in gas environments (in situ). This thesis gives three examples of such studies using microscopy and spectroscopy.

In the last decades, activity-based protein profiling (ABPP) has emerged as a powerful chemical tool that may aid the ever-challenging drug discovery process.

Promotor: Prof.dr. M. Ubbink

Climate change is a challenge for both current and future generations. New biological resources have to be developed in order to meet the demand for energy as well as the demand for food.

Promotor: Prof.dr. G.J. Kroes

Promotor: Prof.dr. H.S. Overkleeft

Een uitgave in de serie Handboeken Veiligheid, waaraan ook Erwin Muller, hoogleraar veligheid en recht bij het Instituur voor Strafrecht & Criminologie , een bijdrage heeft geleverd.

Microglia support the central and peripheral nervous system by forming the first line of defense against hazardous events. Microglia are increasingly acknowledged as critical players in neurodegenerative diseases, highlighting them as potential therapeutic targets.

Promotores: H.S. Overkleeft, G.A. van der Marel, Co-Promotor: R.G. Boot

Artificial photosynthesis has recognised potential to produce green and sustainable fuels from earth-abundant resources such as water, carbon dioxide (CO2), and sunlight.

Promotores: H.S. Overkleeft; G.A. van der Marel Co-Promotor: B.I. Florea

Hydrogen peroxide (H2O2) is an important bulk chemical that is used in various industrial processes. More than 95% of the H2O2 used in industry is made via the anthraquinone process during which a large amount of energy is going to waste.

Promotor: Prof.dr. J.G.E.M. Fraaije, Co-promotor: A. Kros

Al het onderzoek van de Universiteit Leiden is georganiseerd in instituten. Om recht te doen aan de veelkleurigheid van het onderzoek (en dus ook aan het onderwijs) dat daar uit voortvloeit vindt u op deze pagina’s omschrijvingen van alle Leidse instituten.

In order to be able to develop effective medicine and treatments to prevent or cure autoimmune diseases or cancer we need to understand the mechanisms how they arise and what drives their course.Unravelling the fundamental molecular mechanisms influencing the onset and course of diseases such as allergies,…

Glycoconjugate vaccines are composed of microbial poly- or oligosaccharides covalently linked to a carrier protein.

Synthetic hydrogels that mimic the natural extracellular matrix in the biophysical and biochemical cues it provides to cells are in high demand, however the cell phenotypes as they are observed in vivo in numerous cases have yet to be attained.

This thesis systematically studies the physicochemical properties of non-planar, propeller-shaped, polycyclic aromatic hydrocarbons. The synthesis of several so-called propellerenes is described on a gram scale, using optimized procedures aimed at using less hazardous reagents and reducing the amount…

Large parts of the research described in this Thesis aims at the development of oligopeptide-masked toxins and their in situ immunoproteasome-mediated activation.

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.

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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As a virtually inexhaustible source, solar energy plays a major role in future global energy scenarios.

Multicopper oxidase, laccase, can efficiently reduce oxygen to water and are mostly used in the enzymatic biofuel cells.

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…

Promotor: E. Bouwman, Co-promotor: S. Bonnet

Leiden en Delft zijn zeer geschikt om de MST te combineren met persoonlijke ontwikkeling en te werken aan jouw toekomst.

Chapter 2 describes a post-synthetic methodology to introduce a fluorescent label in highly lipophilic, Pam3Cys based conjugates.

In the search for sustainable energy solutions, the idea of artificial photosynthesis has been proposed as an approach with which to use water and sunlight to produce hydrogen.

Microbial rhodopsins are photosensitive pigments implemented in the growth and adaptation of a large population of microorganisms.

Bacteria often experience external challenges, such as changes in environmental conditions or attacks by bacteriophages.

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.

Before the large scale use of renewable energy sources can be implemented in our society, the storage of electrical energy needs to be tackled. Storage the energy as hydrogen via the reduction of protons is a good option.

In this thesis, the discovery and optimization is described of chemical tools to study the N-acylethanolamine (NAE) biosynthetic pathway.

Promotor: Prof.dr. H.J.M de Groot, Co-Promotor: A. Alia

Nanodiscs are small, disc-shaped structures designed to mimic biological cell membranes, composed of a lipid bilayer stabilized by scaffold proteins. Membrane proteins play crucial roles in essential processes such as nutrient and waste transport, molecular recognition, and cell signalling, making them…

Promotor: Prof.dr. H.J.M de Groot, Co-Promotor: A. Alia

Promotor: Prof.dr. E. Bouwman, Co-Promotor: S. Bonnet

Promotor: Prof.dr. E. Bouwman, Co-promotor: S. Bonnet

The glycosylation reaction is a pivotal reaction in creating new and complex oligosaccharides.

Promotores: Prof.dr. H.J.M. de Groot, Prof.dr. J. Matysik (Universitaet Leipzig)

Less than 1 in 10 drug candidates that enter phase 1 clinical trials actually gets approved for human use.

Promotor: Prof.dr. E. Bouwman, Co-promotor: S. Bonnet

Promotores: Prof.dr. H.S. Overkleeft, Prof.dr. G.A. van der Marel

Understanding how nature captures and transfers solar energy is essential both for elucidating biological photosynthesis and for guiding the design of artificial light-harvesting systems.

The cellular metabolism of immune cells constitutes an important part of their proper function and activation. Using T cells as an example, this phenomenon is highlighted by the metabolic reprogramming that occurs in these cells upon activation.