Pseudomonas Aeruginosa is a Gram-negative bacterium which can form biofilms, increasing its resistance against antibiotics and the host immune system. Polysaccharides are an integral part of this biofilm, one of these polysaccharides is called Psl. PslG is a glycosidase, able to cleave this polysaccharide,…

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

Glycosidases (GHs) are enzymes responsible for the degradation of carbohydrates and play many roles in human health and pathophysiology. Often, abnormal levels of glycosidase activity are markedly linked to human pathologies.

This thesis describes the synthesis, analysis of various tetrazine bearing compounds and use in bioorthogonal chemistry.

This thesis focuses on developing new chemical synthesis strategies to produce native ADP‑ribosylated biomolecules with precise structural control.

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

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

This thesis systematically studies the physicochemical properties of non-planar, propeller-shaped, polycyclic aromatic hydrocarbons. The synthesis of several so-called propellerenes is described on a gram scale, using optimized procedures aimed at using less hazardous reagents and reducing the amount…

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 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.

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).

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

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…

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

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

In this thesis an activity-based probe was discovered that could visualize the activity of PLAATs. With an optimized gel-based ABPP assay in hand, screening of a compound library led to the discovery of alpha-ketoamides as a hit for PLAAT3.

Promotor: Prof.dr. H.S. Overkleeft

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

In order to be able to develop effective medicine and treatments to prevent or cure autoimmune diseases or cancer we need to understand the mechanisms how they arise and what drives their course.Unravelling the fundamental molecular mechanisms influencing the onset and course of diseases such as allergies,…

Promotor: Prof.dr.ir. E. Deprettere

Chemische stoffen maken, om biologische vragen mee op te lossen. Wouter van der Linden vat even kort de chemische biologie samen. Daaraan levert hij zijn bijdrage met stoffen die uiteindelijk behulpzaam zijn in de strijd tegen kanker: ‘Dus niet de medicijnen zelf, maar een chemische gereedschapskist…

Cholesterol influences many pathways, including serving as precursor for adrenal steroidogenesis. Imbalance of cholesterol levels has been implicated in several diseases including cardiovascular diseases and its underlying pathology, atherosclerosis.

Promotor: Prof.dr. A.P. IJzerman, Co-Promotor: L.H. Heitman

Adenosine diphosphate ribosylation (ADP-ribosylation) is a fascinating post-translational modification (PTM) that plays a role in a variety of cellular processes and is associated with several diseases, including cancer and viral infections.

This Thesis focuses on the design and synthesis of ADP-ribosylated compounds that can be applied in biological studies.

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

Less than 1 in 10 drug candidates that enter phase 1 clinical trials actually gets approved for human use.

Op voordracht van prof.dr. Roderich Suessmuth van de Technische Universiteit van Berlijn ontving prof.dr. Herman Overkleeft de Friedrich Wilhelm Bessel Research Award. Van Overkleeft is in Leiden verbonden aan het Leiden Institute of Chemistry, LIC/Bio-organic Synthesis.

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.

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

This thesis focuses on the synthesis, characterization and performance towards CO2 electroreduction of mono and bi-metallic particles based on p-block metals

To this day, all cyclophellitol-based inhibitors and ABPs have been close analogues of their natural substrate counterparts. As a result, these probes showed high selectivity towards their target glycosidases.

The glycosylation reaction is a pivotal reaction in creating new and complex oligosaccharides.

Prof. Hermen Overkleeft is bekroond met de 2015 Jeremy Knowles Award van de Royal Society of Chemistry voor zijn innovatieve en inzichtelijke ontwikkeling van activity-based eiwit probes voor de beeldvorming en de identificatie van enzymen in gezondheid en ziekte. Van Overkleeft is in Leiden verbonden…

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

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

Glycosidases are important enzymes in the turnover of polysaccharides and glycoconjugates, and are involved in a range of human pathologies including genetic disorders such as Gaucher and Pompe disease, but also in various cancers.

The aim of this thesis is to explore the use of Bioorthogonal Antigens to study the cross-presentation pathway.

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

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

Utilizing the polymeric platform of polypept(o)ides, this thesis describes synthesis and investigation of novel triblock copolymers to obtain carrier systems with multiple compartments for efficient siRNA delivery. Although the individual microstructure of nanoparticles differs depending on the polymeric…

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.

A key step in the synthesis of oligosaccharides and glycoconjugates is the formation of the glycosidic bond.

Thesis focused on uncovering the underlying mechanisms of the lysosomal storage disorders Gaucher's disease using chemical tools, biochemical assays and lipidomics.

In this thesis the combinatorial use of bioorthogonal labelling and Electron Microscopy (EM)-based imaging techniques is explored to enable observations of specific molecular targets in their ultrastructural context within the cell.

Professor Hermen Overkleeft ontvangt de prestigieuze Roy L. Whistler International Award 2024 van de International Carbohydrate Orgasation. De prijs is een erkenning voor Overkleefts bijdrage aan de koolhydraat- en biochemie.

This thesis describes the development of a variety of mannosylated conjugates. Antigen presenting cells bear mannoside recognizing receptors that actively transport antigen into the cell. This thesis exploits this feature for the development of improved vaccines.

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.