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.

The chemical synthesis of inhibitors and probes targeting endo-glycosidases.

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

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

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

Het chemische biologie-onderzoek bij het Leids Instituut voor Chemisch Onderzoek (LIC) is gericht op het begrijpen van biologische processen op moleculair niveau, om zo onze kennis te vergroten over gezondheid en ziekte van de mens.

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

The main subject of this thesis is the design and synthesis of paramagnetic molecules for protein studies with NMR and EPR spectroscopy.

Overkleeft

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.

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

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

The cannabinoid receptor type 2 (CB2R) is associated with several inflammatory diseases with an unmet medical need (e.g. Alzheimers, multiple sclerosis, reumatoid arthritis). Development of new chemical biology strategies to study this protein is essential to aid future development of drugs for these…

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

At the moment, over 350.000 chemicals are registered worldwide for production and use. Their application, however, may harm human health and the environment.

Chemical-induced organ toxicity is a major concern in the development and use of chemicals, including drugs, pesticides, industrial chemicals and cosmetics. In the last decades, the onset and progression of chemical-induced organ toxicity has been linked amongst others to perturbation of mitochondri…

Promotores: H.S. Overkleeft, G.A. van der Marel, Co-Promotor: R.G. Boot

The inverse electron demand Diels-Alder (IEDDA) pyridazine elimination emerged in 2013 as a new bioorthogonal reaction and constitutes a prime example of what is now known as dissociative bioorthogonal chemistry. The research described in this Thesis aims to develop synthetic strategies which enable…

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.

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

Lysosomal glycosidases are acid hydrolases that fragment glycoconjugates in lysosomes.

Promotie

This thesis has described novel synthetic methods to produce a variety of (glyco)peptides and their application in the study of various immunological processes.

In this thesis, the discovery and optimization is described of chemical tools to study the N-acylethanolamine (NAE) biosynthetic pathway.

This thesis presents the first synthetic peptides ADP-ribosylated on serine, threonine, tyrosine, arginine and cysteine.

This thesis addresses the chemical processes that determine the compositions of giant planet atmospheres.

Promotores: Prof.dr. H.S. Overkleeft, Prof.dr. G.A. van der Marel

Stelt

Sphingolipids are important membrane compounds with a variety of functions. In mammalian cells, different enzymes are involved in the metabolism of sphingolipids, but interruption of this metabolism process leads to different diseases.

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.

Overkleeft Aerts

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

Promotores: T. Hankemeier; R. Berger, Co-promotor: R.J. Vreeken

Plants produce an astonishing variety of secondary metabolites (SMs) which are thought to play vital roles in the fitness of plants through ecological interactions.

Promotor: P.G.L. Klinkhamer, Co-Promotores: K. Vrieling, P.P.J. Mulder

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…

Kasteren

Promotor: E. F. van Dishoeck, Co-promotor: C. Walsh

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

The focus of the described research in this thesis is on the oxidative stress response (Nrf2 pathway). The aim of the research presented in this thesis is to obtain more information concerning microRNAs which are involved in the Nrf2 pathway, to determine and evaluate the application of microRNAs for…

Overkleeft

Promotor: Jelle S. Kaastra Co-promotor: Jelle de Plaa

The ongoing increase in antimicrobial resistance combined with the low discovery of novel antibiotics is a serious threat to our health care.

Wiskunde en Natuurwetenschappen, Leids Instituut voor Chemisch Onderzoek (LIC)

Wiskunde en Natuurwetenschappen, Leids Instituut voor Chemisch Onderzoek (LIC)

How can we, together international experts, define future needs of R+D contributions for innovations in the field of risk-based management of chemicals and products in a global perspective using alternative testing strategies to minimize animal tests?

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

This thesis describes the use of an activity-based proteomics method to study the endocannabinoid system.

Hoe kan de methode om de gecombineerde effecten van metaal-gebaseerde chemische stoffetn te bepalen worden verbeterd?

To address the fundamental questions of how life on Earth emerged and how common life may be in the Universe, it is crucial to know the chemical composition of the planet-forming material.