With increasing carbon dioxide levels in the atmosphere and their detrimental effect on the global climate, modern society needs to push for more renewable energy sources. Storing widely accessible and abundant solar energy in chemical bonds in the form of molecular fuel via artificial photosynthesis…

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

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

Humanity stands at a pivotal juncture, facing the dual challenge of environmental sustainability and rapid population growth, projected to exceed 11 billion by century’s end.

Self-assembly is an abundant process in nature and is vital to many processes in living organisms.

The lysosomal β-glucosidase named glucocerebrosidase (GCase) is a retaining β-glucosidase that hydrolyzes the glycosphingolipid glucosylceramide (GlcCer) to ceramide and glucose at acid pH.

The spindle-assembly checkpoint (SAC) is a safety mechanism which secures accurate chromosome segregation during mitosis.

In a typical glycosylation reaction, a donor is activated to form a (variety of) electrophilic species which can react with a nucleophilic acceptor, following a reaction mechanism having both SN1 and SN2 character.

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

Heterogeneous catalysis is essential to many industrial applications. These catalysts are often comprised of supported nanoparticles, which contain various different surface sites.

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…

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.

Metals surfaces form a group of effective catalysts for the reaction of small molecules such as hydrogen (H2).

Promotor: M.T.M. Koper, Co-promotor: L. Juurlink

Promotor: M.T.M. Koper, Co-promotors: A.I. Yanson, L.B.F. Juurlink

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

The mechanism of the electrochemical reduction of dioxygen by a mononuclear pyridylalkylamine copper complex was investigated (see picture). It was shown that in neutral aqueous solution dioxygen undergoes stepwise reduction, wherein hydrogen peroxide plays a key role. The rate constants determined…

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.

Synthesis and application of chemical biology tools to study immunomodulatory signaling lipids.

Phospholipase A/acyltransferase 3 (PLAAT3) and PLAAT4 are enzymes involved in the synthesis of bioactive lipids. Despite sequential and structural similarities, the two enzymes differ in activity and specificity.

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…

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.

Promotor: M.T.M. Koper, Co-promotor: J.B.F. Juurlink

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.

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

In this dissertation iron-based homogeneous catalysts were synthesized, characterized and investigated for water oxidation activity.

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…

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

Voltammetry plays a crucial role in modern scientific research by offering valuable insights into the electrochemical properties of materials, with wide-ranging applications in fields such as materials science, energy storage, corrosion studies, and sensor development.

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.

Alzheimer's disease (AD) is the most frequent neurodegenerative disorder and the primary cause of dementia. The neuropathological features of AD include the occurrence of senile plaques, neurofibrillary tangles, decreased synaptic density, and loss of neurons. An obstacle in the study and treatment…

PNAS publication on protein encounter complexes

In this work, we illustrate unconventional approaches towards the fabrication of edge functionalized graphene nanostructures and bidimensional architectures in polymeric and metallic supports, with an outlook towards molecular sensing devices.

Promotor: J.P. Abrahams, Co-promotor: T. Grüne

The research described in this thesis centered on retaining exo-β-glucosidases implicated in health and disease, in particular the human inherited lysosomal storage disorder, Gaucher disease (GD).

Inspired by natural photosynthesis, perovskite-based photoelectrochemical (PEC) systems are being developed for artificial photosynthesis, aiming to enhance solar-to-hydrogen conversion for green energy.

The aim of this thesis is to develop and study a robust and adaptable scaffold for supramolecular polymer self-assembly in water.

The relative simplicity of the bacterial cell, short generation times and well defined and inexpensive culturing conditions have significantly contributed to our understanding of many complex biological systems. Yet the workings of the bacterial genome, seemingly impossibly compressed within a tiny…

Glycosidases are important enzymes in the turnover of polysaccharides and glycoconjugates, and are involved in a range of human pathologies including genetic disorders such as Gaucher and Pompe disease, but also in various cancers.

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.

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

Protein–protein complexes are formed via transient states called encounter complexes that greatly influence the formation of the stereospecific complex.

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

Monoacylglycerol lipase (MAGL) is the principal enzyme responsible for hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL inhibition provides several potential therapeutic opportunities, including anti-nociceptive, anti-inflammatory and anti-cancer activity.

Promotor: M.T.M. Koper, Co-Promotor: L.B.F. Juurlink

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.

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

As leading cause of death worldwide, cancer is responsible for nearly 10 million deaths in 2020 according to World Health Organization (WHO). Cisplatin and its derivatives are commonly used chemotherapy agents for current cancer treatment in the clinics.

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