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.

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.

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

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.

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.

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.

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

Phosphorylation affects all four major biomolecules – proteins, lipids, carbohydrates and nucleic acids – and plays a pivotal role in the most fundamental cellular functions.

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.

Glycosidases are essential in fundamental biological processes and are responsible for the degradation of most (oligo)saccharides, glycolipids and glycoproteins.

This thesis systematically analyzes the physical-chemistry of lipid-graphene interactions with the major objective of reconciliating the variety of results reported in the literature.

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

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.

Promotores: Prof.dr. G.A. van der Marel, M. van Heel

This thesis describes the design and development of subunit‐selective inhibitors of particular catalytically active subunits of human constitutive proteasomes and immunoproteasomes.

The endocannabinoid receptors CB1R and CB2R are involved in a plethora of processes, and consequently are involved in many pathological conditions. Their wide distribution makes the CBRs both an interesting therapeutic target and hard to study.

Lysosomal glycosidases are acid hydrolases that fragment glycoconjugates in lysosomes.

Advanced sensing techniques require graphene with high quality and well-controlled surface chemistry.

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…

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.

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.

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

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

This thesis describes the use of a combined approach of computational and experimental techniques to gain novel insights to understand the glycosylation reaction and its reactive intermediates.

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

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

All life on earth contains DNA, which is used to store biological information. Organisms compact their DNA in order for it to fit inside their cell(s).

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

Enzymes are innately sensitive to changes in the amino acid sequence, which largely constrains their evolutionary potential, i.e., evolvability. This evolutionary burden can be alleviated in the presence of stabilizing mutations, which increase the buffering capacity of enzymes to tolerate mutations…

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.

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

The research presented in this thesis makes use of small molecules (as H2 , D2 and O2 ) on well-defined single crystal surfaces (flat Pt(111), flat Cu(211) and curved Pt(111)) to elucidate the role of surface structure and degrees of freedom in the reactant in specific surface reactions.

Promotor: Prof.dr. M. Ubbink

This thesis describes the synthesis and biological evaluation of TLR2/6, TLR4, TLR7/8 and TLR9 ligands, of which the activity can be conditionally controlled.

This thesis is concerned with the constitution of chiral responsive matrix assemblies that may undergo light-driven conformational changes and self-select vibrations to develop vibronic states for driving semi-classical coherent transfer with nearly 100% yield in a lossless NCAP process.

Antibiotic resistance, caused by widespread use of antibiotics, leads to bacterial infections that are difficult, if not impossible, to treat and is a major worldwide health concern.

Actinobacteria are well known for the production of bioactive natural products, many of which have applications in the fields of human, animal and plant health. Subject of this thesis are the anthracyclines, glycosylated aromatic polyketides with potent anticancer activity.

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…

Promotor: A. Kros

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.

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.

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

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.

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.

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.

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…

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