The Chemical Probe Facility is part of the Leiden Early Drug Discovery & Development (LED3) center. Activity-based protein profiling (ABPP) is one of the pillars of chemical biology. ABPP determines the activity of entire protein families in living cells and tissues under physiological conditions, such…

Chemical biology research at the Leiden Institute of Chemistry is aimed at understanding biological processes at the molecular level to strengthen the knowledge base of human health and disease. The approach to achieve this goal is a fundamental chemical one; with the aid of chemical probes biological…

Chemical biology research at the Leiden Institute of Chemistry is aimed at understanding biological processes at the molecular level to strengthen the knowledge base of human health and disease. The approach to achieve this goal is a fundamental chemical one; with the aid of chemical probes biological…

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.

Chemical biology research aims at understanding and manipulating biological processes at the molecular level. Physiological processes that are behind human disease are subject of detailed chemical biology studies with the aim to identify new drug targets, but also leads for drug development or that…

The theoretical explanation of cosmic acceleration is nowadays one of the biggest puzzles in cosmology.

Chemical tools to monitor drug-target engagement of endogenously expressed protein kinases are highly desirable for preclinical target validation in drug discovery. Here, we describe a chemical genetics strategy to selectively study target engagement of endogenous kinases.

Issues such as climate change, the depletion of natural resources or social inequality are too complex to be addressed from a single scientific discipline or by a single country. Leiden University has the expertise to bring the resolution of these enormous problems a small step closer.

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.

To address biological questions related to human health, chemical tools are essential. Covalent or non-covalent interactions of compounds with biomolecules offer a range of possibilities for study. They can be used to identify enzymes based on their activity, to influence cellular regulation, by changing…

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

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.

The LED3 Network, consisting of researchers from the Leiden Institute of Chemistry (LIC), the Institute of Biology Leiden (IBL) and the Leiden Academic Centre for Drug Research (LACDR), is very excited to organise the “LED3 Chemical Biology Talks”. This lecture series brings excellent researchers in…

Overkleeft

This thesis described the development of novel scanning tunneling microscopy techniques to investigate strongly correlated electronic states in quantum matter.

Overkleeft

How can we develop new chemical biology tools and approaches to understand and interfere with glucosylceramide metabolism in relation to Gaucher disease?

Lecture

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

Luris

Science, Leiden Institute of Chemistry (LIC)

Lysosomal glycosidases are acid hydrolases that fragment glycoconjugates in lysosomes.

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

Science, Leiden Institute of Chemistry (LIC)

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…

It is an established fact that the Standard Model has to be extended to explain the so-called Beyond the Standard Model (BSM) phenomena: dark matter, matter-antimatter asymmetry of the Universe and neutrino flavour oscillations.

The Standard Model (SM) of particle physics fails to explain several observed phenomena and is incomplete. In order to resolve this problem, one may extend the SM by adding new particles.

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

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…

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

Lecture

Promotor: Prof.dr. J. Schaye, Co-promotor: Marcello Cacciato

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

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

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…

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

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

Lecture

LED3 is the combined effort of three excellent institutes of Leiden University. Through joined hands, we are able to give rise to a more effective early drug discovery pipeline. Let us briefly introduce the three institutes.

Ramautar

Diacylglycerol lipases (DAGLα and DAGLβ) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo.

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…

PhD defence

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