Biopolymer sequencing with graphene edge-based tunnel junctions has the potential to overcome current limitations with the third generation of sequencing based on biological nanopores.

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

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…

The main subject of this thesis is the design and synthesis of paramagnetic molecules for protein studies with NMR and EPR spectroscopy.

The aim of the research presented in this thesis was to develop new methods forchallenging systems in liquid-state NMR using paramagnetic effects generated by thetwo-armed probe CLaNP-5.

Promotor: Prof.dr. J.P. Abrahams, Co-Promotor: N.S. Pannu

The research aims to explore the evolutionary adaptability of enzymes and the impact of temperature on protein evolution pathways, using M. tuberculosis β-lactamase BlaC as the object of study. Enzymes inherently embody a delicate balance between activity and stability, and the acquisition of new enzymatic…

This Thesis focuses on the design and synthesis of ADP-ribosylated compounds that can be applied in biological studies.

Climate change is one of the largest challenges faced by humanity. To combat this research into alternatives to fossil fuels is ongoing. Dihydrogen is considered a good alternative fuel, since its burning only forms water.

The focus throughout this thesis will be on gathering fundamental studies of the detailed structure and composition of the electrode/electrolyte interface effect on the rate and mechanism of key electrocatalytic reactions.

Promotor: Prof.dr. J.P. Abrahams, Prof.dr. M. van Heel

Cardiovascular diseases (CVDs) are the leading global cause of mortality. Endothelial dysfunction, an early reversible stage of CVD development, is marked by decreased nitric oxide production linked to Ca2+ influx in endothelial cells.

This thesis describes the use of bioorthogonal proteins in immunological settings. It provides an introduction towards the field of protein modification, which was used throughout the thesis for the expression of proteins containing unnatural amino acids.

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

Promotor: A. Kros

Producing green energy has become the main goal in our society in the search of reducing or eliminating the carbon emission from fossil fuels.

Solar energy harnessed by plants and algae has great potential to be converted into biofuels for future generations.

Due to their central physiological roles in living organisms, retaining beta-glycosidases have been the subject of tremendous research efforts to examine their structure/function relation using numerous biophysical and biochemical approaches.

Aspergillus niger is an important industrial producer of organic acids and enzymes producing large amounts of spent fungal biomass.

Catalysis is of extreme relevance in the production of everyday materials and plays a central role in many aspects of our life.

Several single-stranded RNA viruses make use of Xrn1-resistant RNAs in their 3’ untranslated regions of their genome RNAs in order to increase their pathogenicity.

The redox-conversion reaction of metal-disulfide and metal-thiolate complexes are important, as they may shed light on electron-transfer reactions that often occur in Nature.

This thesis describes the design and synthesis of fragments of various cell wall carbohydrates of the Streptococcus species, including the branched Group B-specific antigen (GBC) of Group B Streptococcus, glycerol phosphate (GroP) modified group A carbohydrate (GAC), and the O-acetylated type 1 capsular…

Sustainable energy from wind and solar is most readily available near the sea.

Advanced mass spectrometry of glycosphingolipids takes the central stage in this thesis. Investigations focus on characterization of glycosphingolipid metabolism in health and disease with emphasis to the detection and accurate quantitation of known and so far unknown glycosphingolipids and closely…

Global healthcare is on the verge of an antibiotic availability crisis as bacteria have evolved resistance to nearly all known antibacterials. Identifying new antibiotics that operate via novel modes-of-action is therefore of high priority.

The first steps are made in personalised cancer vaccination strategies, which aim to induce a more specific immune response with fewer side effects. The activation of cytotoxic T cells is crucial for an effective immune response.

Supramolecular polymers are class of materials that are formed by non-covalent interactions such as hydrogen bonding, π-π interactions, electrostatic interactions and the hydrophobic effect.

This thesis describes biochemical investigations of glucocerebrosidase (GBA), the lysosomal β- glucosidase that is deficient in Gaucher disease (GD).

In the current global context, there is a pressing need to address sustainable energy supplies to safeguard our Planet and its ecosystems. The choices made by human society have a significant impact on genetic evolution and climate.

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

Carbohydrates, or sugars, are the most diverse and most abundant biomolecules known. However, the isolation of carbohydrate samples in sufficient amounts and purity is often impractical or even impossible, so the chemical synthesis of glycosides becomes relevant. The glycosylation reaction, in which…

Membrane fusion is a vital process in living organisms and is mediated by zipper-like proteins.

Tin electrodeposition applications have rapidly evolved in the past 25 years.

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 work describes several studies into the electroreduction of carbon dioxide (CO2RR), both regarding mechanistical aspects and catalyst stability considerations. Mechanistic insights into carbon-carbon bond formation on a silver catalyst are described in Ch 2, were we find an acetaldehyde-like surface…

Pseudomonas Aeruginosa is a Gram-negative bacterium which can form biofilms, increasing its resistance against antibiotics and the host immune system. Polysaccharides are an integral part of this biofilm, one of these polysaccharides is called Psl. PslG is a glycosidase, able to cleave this polysaccharide,…

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

Glycoside hydrolases (glycosidases/GHs) are widely abundant enzymes in all kingdoms of life and are important biocatalysts that catalyze the hydrolysis of glycosidic linkages in oligo/polysaccharides, glycoproteins and glycolipids with tremendous efficiency

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.

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.

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.

Advanced UHF MRI techniques provide powerful tools for studying the zebrafish brain, an emerging model in neurological research. In this work, various MRI and localized MRS methods are optimized and employed for UHF strength for studying the zebrafish brain.

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.

Heterogeneous catalysis is one of the fundamental processes of modern life, being common in industrial refinery and hydrogen vehicles, all the way to the living cell. The dissociation of H2 on Cu(111) is an important benchmark system for studying heterogeneous catalysis, with a large and varied amount…

The goal of the research presented in this thesis was to explore the chemical space of ruthenium(II) photocages, investigate their ability to host potent chemotherapy drugs, and to red shift the activation wavelength of the most promising PACT candidates to conduct biological studies.

Promotor: Jaap Brouwer, Co-promotor: Remus Th. Dame

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