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

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

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

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

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

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

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.

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

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.

Promotor: Huub J.M. de Groot, Co-promotor: Francesco Buda

Promotor: H.S. Overkleeft, J. Neefjes, Co-promotor: M. van der Stelt

Promotor: Prof.dr. G.J. Kroes

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.

Decentralized plug and play systems for energy production are the future picture of our society. Artificial photosynthetic systems are used for this purpose.

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

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.

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

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

Metal-based prodrugs based on ruthenium(II) polypyridyl complexes have proven to be very suitable for application in both photodynamic therapy (PDT) and photo-activated chemotherapy (PACT).

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…

Synthetic cells, also known as artificial cells or protocells, have wide ranging applications from drug delivery vectors to cell models. In biotechnology they can function as micro- or nanoreactors with possible applications in biocatalysis and photocatalysis. Phospholipids are by far the most commonly…

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

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

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

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,…

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

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: H.S. Overkleeft, Co-promotor: B.I. Florea

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

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

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.

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

Glycosidases are essential in fundamental biological processes and are responsible for the degradation of most (oligo)saccharides, glycolipids and glycoproteins.

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Phosphorylation affects all four major biomolecules – proteins, lipids, carbohydrates and nucleic acids – and plays a pivotal role in the most fundamental cellular functions.

This thesis studies theoretical surface chemistry within the field of heterogeneous catalysis.

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.

Conference

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…

Leiden University encourages all its laboratories to obtain LEAF (Laboratory Efficiency Assessment Framework) accreditation.

Through metabolism, biochemical processes give rise to the complexity of life. Acquired and inborn errors in metabolism underlie many diseases occurring in man. The challenge for present day medical biochemistry is to find, and integrate, pieces of information at molecular, cell and organismal level…

The Leiden Academic Centre for Drug Research (LACDR) is a centre of excellence for multidisciplinary research on drug discovery and development.

It is estimated that approximately 30% of all proteins require a metal to function. Investigating the relationship between metal-binding and peptide/protein folding allows us to uncover fundamental rules for creating metallo-peptides and proteins, which in turn leads to the creation of new structures,…

The central theme of Rik Mom’s research group is to identify what the electrode-electrolyte interface looks like when electrocatalysis is taking place. Using specialized forms of Raman and X-ray spectroscopy, we study the chemical state and bonding environment of the electrode surface and near-surface…

Chemical reactions go hand-in-hand with an energy exchange with the environment in which they take place. Surfaces offer a variety of energy dissipation channels, constituted by the nuclear and electronic degrees of freedom of the atoms at the interface. Aiming at an improved future harvesting of energy,…

The CIGR comprises research groups from the Leiden Institute of Chemistry (LIC), the Leiden Academic Centre for Drug Research (LACDR) and the Leiden Institue of Physics (LION).

This thesis describes the synthesis, analysis of various tetrazine bearing compounds and use in bioorthogonal chemistry.

The close interaction between organic chemi stry and biology goes back to the late 18th century, when the modern natural sciences began to take shape. After synthetic organic chemistry arose as a discipline, organic chemists almost immediately began to pursue the synthesis of naturally occurring compounds,…