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

Within this thesis the central stage is taken by the discovery and investigation of transglycosylation of sterols. First, investigation focuses on the development of a method to accurately detect and quantify glucosylated metabolites in biological materials.

This thesis describes research aimed at discovering inhibitors selective for either of the two endoplasmic reticulum α-glucosidases, ER-I and ER-II, with the overarching goal of discovering new antiviral agents to treat viruses that rely on host N-glycosylation for proliferation.

Hydrocarbonylation of alkenes with carboxylic acids in synthesis of carboxylic acid anhydrides is relatively less explored. We herein present a study and optimization of a palladium-catalyzed hydrocarbonylation reaction of alkenes using carboxylic acids as the nucleophile, by which acid anhydrides can…

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

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…

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.

The

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

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…

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…

The work described in this Thesis is focused on the assembly of oligosaccharide fragments derived from a fungal polysaccharide, galactosaminogalactan (GAG) and fragments of the exopolysaccharide Pel, generated by Pseudomonas aeruginosa.

Extending our current arsenal of antibiotics is key to staying ahead in the arms race between humans and resistant bacteria.

The electrochemical hydrogenation reaction is an alternative approach for the transformation of unsaturated bonds without the use of flammable dihydrogen gas.

We review the state-of-the-art in the theory of dissociative chemisorption (DC) of small gas phase molecules on metal surfaces, which is important to modeling heterogeneous catalysis for practical reasons, and for achieving an understanding of the wealth of experimental information that exists for this…

Promotor: H.J.M. de Groot

The confinement of molecular catalysts in metal-organic frameworks has the potential to lead to significant improvements in selectivity, long term activity and catalyst stability.

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

SMR can be used to measure the mass of adsorbed protein to nanoparticles with a high precision in the presence of free protein.

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…

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…

Despite the history of studies on methanol formation from CO2, the dominant elementary reaction steps that constitute the chemical mechanism for this catalyzed process are not determined.

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

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

Marc Koper’s research focuses on electrocatalysis and electrochemical surface science for sustainable energy and chemistry. Reactions of interest are the redox reactions of the oxygen/hydrogen cycle (water oxidation, hydrogen evolution), the carbon cycle (reduction of carbon dioxide, oxidation of small…

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

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.

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.

Lipid nanoparticles (LNPs) have enabled the success of mRNA vaccines but remain limited in broader therapeutic use by challenges in delivery efficiency, targeting, and mechanistic understanding.

The work described in this thesis focuses on the development of linear or cyclized peptide probes against protein N-methyltransferases to characterize their specific binding behavior, providing further binding details for inhibitory activity study.

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

Research question

Supervisor: Gerard van Westen

Discover the admission requirements for the MSc International Organisation at Leiden University in The Hague. Includes 80 ECTS, English test scores (IELTS/TOEFL), and supporting documents.

Can small molecule drugs restore the immune system’s ability to fight tuberculosis by boosting autophagy?

Early time-resolved experiments by Frauenfelder on the ensemble of the kinetic rebinding of CO to myoglobin molecules resulted in a stretched exponential relaxa-tion due to a very large spread of the reaction rates of individual molecules.

This thesis discusses several questions regarding the double ramification cycle as a Chow class on the moduli space of stable n-pointed genus g curves using tools from so-called logarithmic geometry.

G protein-coupled receptors (GPCRs), one of the largest families of membrane proteins, are responsive to a diverse set of physiological endogenous ligands including hormones and neurotransmitters.

Lecture

Lecture

Source: ChemMedChem (2015)

Cytotoxic T-cells (CTLs) are involved in the clearance of viruses and killing of tumor cells.

Chemical tools to monitor drug-target engagement of endogenously expressed protein kinases are highly desirable for preclinical target validation in drug discovery. Here, we describe a chemical genetics strategy to selectively study target engagement of endogenous kinases.

Deficiency of glucocerebrosidase (GBA) underlies Gaucher disease, a common lysosomal storage disorder. Carriership for Gaucher disease has recently been identified as major risk for parkinsonism. Presently, no method exists to visualize active GBA molecules in situ. We here report the design, synthesis…

Active-site directed probes are powerful in studies of enzymatic function. We report an active-site directed probe based on a warhead so far considered unreactive.

The cannabinoid CB2 receptor (CB2R) represents a promising therapeutic target for various forms of tissue injury and inflammatory diseases. Although numerous compounds have been developed and widely used to target CB2R, their selectivity, molecular mode of action and pharmacokinetic properties have…