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

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

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 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

Hydrodesulfurization (HDS) is an ubiquitous part of oil refining that ensures that fuels are cleaned of impurities and environment release of pollutants such as SOx and NOx gasses are minimized.

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

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.

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…

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

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…

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.

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…

Every organisms in the tree of life faces the same challenge: the length of its DNA exceeds the volume of the cell it needs to fit in. Several strategies have evolved to solve this problem, one of them being the expression of proteins that bind and organize the DNA.

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.

Zebrafish is an excellent model organism for studying various human diseases. Due to opaqueness of the adult phase, in vivo studies are restricted to early embryonic stages. This raises the need for rapid sensitive and non-invasive in vivo imaging methods to follow developmental processes, not only…

Twenty years from now, the world population is estimated to be around 8.7 billion people, compared to the current 7.3 billion. In combination with the improvements in living standards and the corresponding growth in consumption, this will result in an enormous increase in the demand for food, consumables,…

PhD candidates carry out a programme of independent research and additional (limited) course work, culminating in production of a PhD thesis in typically 4 years.

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.

This is an Erasmus+ International Credit Mobility project of the Faculty of Sciences with one partner in Ukraine.

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…

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

Leiden University research institutes based in Leiden and The Hague.

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

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.

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…

Solar energy is used by photosynthetic organisms to drive energy required cellular processes. Is absorbed by two groups of pigments, located in the LHCs.

Bicarbonate buffer is largely found in nature due to its ability to regulate pH variations around neutral values. As the pH changes, so does the speciation of the buffer.

This work has described synthetic strategies towards well-defined structures resembling capsular polysaccharide (CPS) fragments, CPS mimics, teichoic acid (TA) fragments as well as a third-generation ring-closing tandem metathesis (RCM) linker to better exploit the potential of automated synthesis.

Schistosomiasis is an acute and chronic disease caused by blood dwelling parasitic trematodes of the genus Schistosoma, and it is classified as the second most socioeconomically devastating parasitic disease, second only to malaria.

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

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

Is there a sufficiently large market for drug screening and testing in Zebrafish larvae using membrane fusion?

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…

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

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.

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

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…

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.

This thesis describes the development and optimization of the first molecular tools to study the enzyme PLA2G4E.

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.

Activity-based protein profiling (ABPP) is a functional proteomics technique for directly monitoring the expression of active enzymes in cell extracts and living cells. The technique relies on irreversible inhibitors equipped with reactive groups (warheads) that covalently attach to the active site…

Promotor: Prof.dr. J. Brouwer, Co-promotor: Dr. Remus Th. Dame

Electrocatalysis allows for storing electricity or converting it into chemical bonds, producing chemical building blocks and fuels using renewable resources.

The main goal of the research described in this thesis was the development of new photoactivated chemotherapy (PACT) ruthenium(II) complexes bearing a non-toxic photolabile ligand.

Vitamin A or retinol is essential in embryonic development, the visual cycle and the immune system.

In this thesis, bioorthogonal chemistry is combined with correlative light-electron microscopy to selectively label and study pathogenic intracellular bacteria within the host immune cell.

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…