De Universiteit Leiden heeft onderzoeksinstituten gevestigd in Leiden en Den Haag.

Hydrogen fuel cells are expected to be pivotal in the energetic transition towards renewable energy sources such as solar and wind power. However, their industrial scalability is severely hindered by the high cost and degradation rate of platinum catalysts, one of their key components. Addressing this…

Microscopic insight on lipid-based nanomedicine in vivo remains limited to the perception of the knowledge that could be obtained: if we interpret only what we see, then we only believe to know. Although believing to know encapsulates an undefined amount of uncertainty in the exploration of lipid-based…

Metal complexes and 2D materials like graphene were combined to produce structures that can function as sensors.

This Thesis describes a strategy to synthesize 1,2-cis-oligosaccharides modulated by additives, such as dimethylformamide (DMF), triphenylphosphine oxide (Ph3P=O) and N-methyl(phenyl)formamide (MPF), using building blocks that carry solely benzyl type protecting groups and are therefore of uniform r…

Ice, the solid state of water, plays an important role on our planet as well as the entire universe.Despite the fact that an individual water molecule has a very simple structure, its chemical bonding in the solid phase can be surprisingly complex.

Nucleoid associated proteins maintain the architecture of the bacterial chromosome and regulate gene expression, hinting that their role as transcription factors may involve local three-dimensional chromosome re-modelling.

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.

β-Lactamases are enzymes that can break down β-lactam substrates, such as antibiotics, preventing the use of these antibiotics for the treatment of various infectious diseases. However, some compounds, β-lactamase inhibitors, can block these enzymes allowing for possible treatments using a combination…

The role of the interfacial environment during electrochemical reactions has been increasingly valued, especially for those reactions involving protons or hydroxyl ions.

The research described in this thesis focused on the use of bioorthogonal antigens to investigate immunological processes in antigen presenting cells. Bioorthogonal antigens are antigenic proteins produced through recombinant expression in a methionine auxotrophic E. coli strain.

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In most applications, electrocatalysts exhibit a large surface area to volume ratio, for example using nanoparticles.

This thesis investigates reactive interfaces in surface science across three domains: heterogeneous catalysis, environmental nanoplastics, and two-dimensional materials.

This thesis focuses on developing wafer-scale two-dimensional (2D) materials by combining synthesis, transfer, characterization, and device integration of graphene, hexagonal boron nitride (h-BN), and BN-doped amorphous carbon.

The studies presented in the work show the potential of the integrative use of biophysical data in defining the structural basis of protein interactions.

Kinase inhibitors are key therapeutic agents, particularly in oncology, yet their clinical efficacy is often hampered by off-target effects and limited understanding of their cellular target profiles.

This dissertation explores new chemical strategies for the synthesis of self-adjuvanting peptide conjugates and immunomodulatory ligands aimed at targeted activation of the immune system.

Neurodegenerative diseases pose a large medical and societal challenge. The etiology of these diseases is still poorly understood, which makes drug discovery for these diseases difficult.

Green hydrogen is produced via a process called water electrolysis. During electrolysis water is split into oxygen and hydrogen.

Single-layer graphene (SLG) has attracted considerable interest as a proton exchange membrane for direct methanol fuel cells (DMFCs), owing to its atomic thickness, mechanical robustness, and unique proton permeability.

This dissertation presents the synthesis and evaluation of antibody recognition for various capsular polysaccharide (CP) fragments of Staphylococcus aureus (S. aureus).

The overall theme of this thesis is to complement the electrochemical data acquired in fuel cell research with in situ X-ray photoelectron spectroscopy (XPS) and soft X-ray absorption spectroscopy (XAS).

A key step in the synthesis of oligosaccharides and glycoconjugates is the formation of the glycosidic bond.

Reducing greenhouse gas emissions is one of the most pressing challenges that humanity faces in the coming decades.

In this thesis, we study different curved single crystals because of the diversity of surface structures across their curvature.

This thesis advances our understanding of lipid uptake, a vital first step in lipid metabolism, by developing innovative click chemistry-based tools to study how immune cells internalize lipids.

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

Studievoorlichting

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, J. Neefjes, Co-promotor: M. van der Stelt

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 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).

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.

Promotor: Prof.dr. H.S. Overkleeft

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

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.

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

Het Gorlaeus Gebouw wordt in drie fasen gerealiseerd. Het nieuwe gebouw is medio 2028 helemaal gereed.

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

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: Prof.dr. G.J. Kroes