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

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.

One of the main challenges in the development of an effective anti-cancer vaccine is the generation of an adequate and directed cellular immune response.

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.

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.

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

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

Overkleeft

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

PhD students at Bio-organic Synthesis are invited to present their work during the weekly Monday Morning Biosyn Talks.

A high-end label: Cyclophellitol aziridine-type activity-based probes allow for ultra-sensitive visualization of mammalian β-glucosidases (GBA1, GBA2, GBA3, and LPH) as well as several non-mammalian β-glucosidases (see picture). These probes offer new ways to study β-exoglucosidases, and configurational…

Three at the same time: a ligation strategy combining tetrazine–norbornene cycloaddition, Staudinger–Bertozzi ligation, and copper(I)-catalyzed click reaction was used to label the three catalytic activities of the proteasome simultaneously in a single experiment. The orthogonality of the three ligation…

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

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

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.

Bachelor and Master students of all chemistry related studies are more than welcome to take part in our research activities. We have projects on design and synthesis of biologically relevant compounds within an ongoing research project. Supervision, following the apprentice/teacher model, is one of…

The Leiden Institute of Chemistry (LIC) is the basis for research and collaborations of the Leiden chemistry groups. Chemistry is the central science enabling a healthy future in a sustainable society. Chemistry researchers at Leiden University take a fundamental approach in finding tailored solutions…

Large parts of the research described in this Thesis aims at the development of oligopeptide-masked toxins and their in situ immunoproteasome-mediated activation.

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

To what extent are there differences between countries in and outside the European Union and the Schengen area in the level of crimmigration, the merger between migration control and crime control, and to what extent can these differences be explained by the way in which state and non-state actors in…

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

The wide-ranging interests of the Dutch archeologist Maurits van Loon -prehistory, art history, and ancient history - are reflected in these papers, which commemorate his 30 years of archeological research in the Near East

All living systems are assembled from nature’s repertoire of small, medium, and large organic molecules. This theme focuses on the study, discovery and development of novel bioactive compounds obtained from biodiversity. We aim for new insights into the role of these molecules in the natural environment,…

The GMP Facility facilitates development and production of Advanced Therapy Medicinal Products (ATMPs) and chemical (peptide) synthesis.

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.

The group of Dr. Roxanne Kieltyka designs and synthesizes molecules that self-assemble into polymeric materials using specific non-covalent interactions. These substrates can be used for numerous applications in medicine ranging from disease detection to cell delivery depending on the (bio)molecular…

The goal of hit discovery is to identify suitable chemical starting points to modulate a drug target. A hit can be, a.o., a small molecule, a protein or mRNA. Hit identification is performed via rational design, genome mining, (targeted) library screening, or in silico approaches.

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

Nicotinamide adenine dinucleotide (NAD+) is the substrate used for the introduction of the ubiquitous and highly dynamic PTM in which either one or multiple adenosine diphosphate ribose (ADPr) moieties are covalently attached to a nucleophilic side chain of an specific amino acid in the target protein…

Photocatalysis has emerged as a powerful tool for enabling challenging transformations in organic synthesis. This thesis explores the development of several photocatalytic reactions designed to form carbon-heteroatom bonds from less-functionalized precursors.

This synthesis brings together strands developed in the four studies, sets out memories of the Revolt and presents the Low Countries as a case study.

Research at the MCBIM group is comprised of the following research themes:

The Delivery of Biotherapeutics research group is led by Prof. Matthias Barz and focusses on the synthesis and characterization of polypept(o)ids and their application in nanomedicine to improve existing therapies or enable novel diagnostic or therapeutic approaches.

The close interaction between organic chemi stry and biology goes back to the late 18th century, when the modern natural sciences began to take shape. After synthetic organic chemistry arose as a discipline, organic chemists almost immediately began to pursue the synthesis of naturally occurring compounds,…

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

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.

Carbohydrates, alongside proteins and nucleic acids, constitute a crucial and versatile family of biomolecules present in all life forms. They manifest as monosaccharides, oligosaccharides, and polysaccharides, covalently bonded to proteins and fats. Carbohydrates are integral to plant and arthropod…

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

Despite being the second largest transmembrane protein family after GPCRs, the SLC superfamily has only gained significant attention in early drug development over the past decade.

Cathodic corrosion for producing nanoparticles was (re)discovered when trying to control the electrochemical etching of a scanning tunneling microscopy (STM) tip.

Source: J Med Chem, Volume 57, Issue 8, pp. 3213-22 (2014)

Speech Prosody is the biennial meeting of the Speech Prosody Special Interest Group (SProSIG) of the International Speech Communication Association (ISCA).

The primary goal of this research is to deepen our understanding of substrate-enzyme interactions in Glycoside hydrolases. For this purpose, Bacillus circulans xylanase (BcX) has been selected as a well-established model to examine the Michaelis complex and glycosyl-enzyme adduct.

The neolithization of the southern Netherlands in an antropological and geographical perspective

The research contained in this dissertation explores the origins of fire making in prehistory, focusing primarily on the fire use practices and fire production capacities of Neandertals.

This thesis tackles the urgent challenge of antimicrobial resistance (AMR) through the design of novel antibacterial agents.