The research described in this Thesis was aimed at designing and synthesizing nature-inspired compounds as part of TB vaccine discovery.

This thesis focuses on the design and synthesis of activity-based probes and inhibitors targeting enzymes involved in the degradation of specific plant glycans.

Promotors: Prof.dr. E. Bouwman, Prof.dr. E. Drent

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

The research presented in this thesis explores the chemotherapeutic potential of metal-based compounds as chemotherapy agents, with an initial focus on the synthesis and DNA interaction studies of platinum and palladium compounds utilizing the [Pt(bapbpy)]2+ scaffold. The study identifies intercalation…

Light-Harvesting Complex II (LHCII) is responsible for light absorption and excitation energy transfer in plants and photosynthetic algae, while in high light it undergoes conformational changes by which it quenches excitations to prevent photodamage.

Nature uses a special class of histone proteins, histone variants, to modulate the properties of chromatin at defined genomic locations.

This Thesis describes the design, synthesis and evaluation as glycoprocessing enzyme inhibitors of focused libraries of iminosugars.

This thesis focused on the exploration of monolayer graphene as a membrane in direct methanol fuel cell (DMFC) applications, with improvements achieved through plasma exposure or damage- free chemical functionalization.

Promotor: Prof.dr. J.P. Abrahams

Promotor: Prof.dr. M. Ubbink

Molecular complexes can be used as electrocatalysts for oxygen reduction, water oxidation, and/or hydrogen peroxide production.

This thesis investigates the relations between metabolism and anatomy through the use of Magnetic Resonance Imaging (MRI).

Promotor: Prof.dr. M.T.M. Koper, Co-Promotor: F. Calle-Vallejo

The thesis focuses on synthesis strategies in oligosaccharide campaigns, and the influence of protecting groups.

Indonesia is experiencing various environmental challenges related to its fast economic growth. Therefore, it is necessary to have measurable and applicable indicators to obtain accurate data and information regarding the costs of adverse environmental impacts arising from economic activities to support…

This thesis introduces the concept of

N-acylethanolamines (NAEs), including N-arachidonoylethanolamine (anandamide, AEA), N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA), are signaling lipids that play an important role in different physiological process.

The work in this thesis has been focused on two subjects. The first is the assembly of alginate oligosaccharides and the generation of building blocks for the enzymatic synthesis of alginate, and the second is the total synthesis of large fragments of the zwitterionic SP1 polysaccharide.

Promotor: M. Ubbink, Co-Promotor: R. T. Dame

A new type of tripodal squaramide-based supramolecular hydrogels is developed and studied.

This doctoral thesis is an effort to understand how lipid phase-separation induced by diacylglycerol analogues in lipid-based nanoparticles affects their in vivo behavior, leading to specific nanoparticle-protein communications and selective cell targeting.

This thesis describes the design, synthesis, and immunological evaluation of varying (neo)antigenic peptide conjugates containing either a TLR2 or a TLR7 agonist.

The disease acute myeloid leukemia (AML) is characterized by fast progression and low survival rates.

Hoe beter de behandeling van gedetineerden, hoe effectiever de gevangenisstraf, zo blijkt. Leidse criminologen onderzoeken daarom hoe detentie kan worden verbeterd, onder meer op gebied van leefklimaat en contact tussen gedetineerden en hun kinderen.

De faculteit biedt een internationale academische omgeving met 36% van de studenten, promovendi en onderzoekers uit het buitenland.

Hoe helpen lipasen in Mycobacterium tuberculosis de bacterie te overleven, en kunnen we deze enzymen gebruiken als doelwit voor nieuwe antibiotica?

Kunnen kleine moleculen het immuunsysteem herstellen en helpen tuberculose te bestrijden door autofagie te stimuleren?

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.

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

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.

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 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.

Lysosomal glycosidases are acid hydrolases that fragment glycoconjugates in lysosomes.

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.

Kinase inhibitors are key therapeutic agents, particularly in oncology, yet their clinical efficacy is often hampered by off-target effects and limited understanding of their cellular target profiles.

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

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.

Despite the fact that gold nanoparticles (GNPs) are one of the most studied nanoparticles, there is still a necessity for new approaches allowing for effective protective coating to enable wider use of GNPs in biomedical applications.

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

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…

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.

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.

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

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.

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.

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

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…