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

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

In the last decades, activity-based protein profiling (ABPP) has emerged as a powerful chemical tool that may aid the ever-challenging drug discovery process.

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.

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

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,…

Activity-based protein profiling (ABPP, also termed chemical proteomics), is one of the pillars of chemical biology, and at LED3 we have taken it to the next level. ABPP allows the assessment of protein function in live cells and tissues, which means that the activity of a complete protein family can…

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

Activity-based protein profiling (ABPP) is a functional proteomics technique for directly monitoring the expression of active enzymes in cell extracts and living cells. The technique relies on irreversible inhibitors equipped with reactive groups (warheads) that covalently attach to the active site…

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

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

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

The drug BIA 10-2474 inhibits fatty acid amide hydrolase (FAAH), a lipase that degrades a specific endocannabinoid. On the basis of this activity, BIA 10-2474 was being developed as a potential treatment for anxiety and pain. In a phase 1 trial of the drug, one subject died, and four others suffered…

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…

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

Lysosomal glycosidases are acid hydrolases that fragment glycoconjugates in lysosomes.

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.

A model method: A strategy that combines a knowledge-based in silico design approach and the development of novel activity-based probes (ABPs) for the detection of endogenous diacylglycerol lipase-α (DAGL-α) is presented. This approach resulted in the rapid identification of new DAGL-α inhibitors with…

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

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

What are the values that Leiden University cherishes? What does the University stand for and what does it consider important?

The philosophers at the Institute of Philosophy develop new perspectives and insights not only on fundamental philosophical questions, but also on topical and interdisciplinary themes such as secrecy, migration, and climate change.

Leiden University has been an international university from its founding in 1575.

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

Students are educated to become academic professionals and responsible and engaged citizens who are internationally and interculturally competent

PhD Defence

The reintegration of high profile ex-offenders frequently receives great political and public attention. While this attention, more often than not in the form of negative sentiments, may be understandable from a moral perspective, it raises several important questions: how do such offenders reintegrate…

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

Supervisor: Anna Vlachodimou

Due to the fact that the Frisian lands lacked major political centers in the Middle Ages and also because most of its monasteries suffered complete destruction in the second half of the 16th century, relatively few written documents concerning medieval Frisian history have survived. To analyze them…

Politically speaking, the Frisian coastal area constitutes a special case in late medieval Europe since it was not subject to an overlord as it withstood feudalization in the 13th century. Its many sub regions, which were dominated by elites of small noblemen and freeholders, long time succeeded in…

A research team from Radboud University and Leiden University, led by senior researchers Prof. Masja van Meeteren (RU/UL), Dr Paul Mutsaers (RU) and Prof. Maartje van der Woude (UL), will examine what national and international research has really found about ethnic profiling by the police.

Promotor: Prof.dr. T. Hankemeier, Co-Promotor: R.J. Vreeken

The key question addressed in this family study is whether the psychophysiological and neurocognitive abnormalities often reported in SAD patients are heritable and can thus be found in family members of SAD patients as well. Determination of heritability of these deficiencies is essential for endophenotyping.…

Supervisor: Maarten Doornbos

Molecular Physiology is a research group at the Leiden Institute of Chemistry, headed by Prof. Mario van der Stelt. The research aim is to design, synthesize and apply new chemical tools to answer important biological and medical questions. We use activity-based protein profiling, assay development,…

Since my master's thesis on the landed property of the Frisian monasteries in the Middle Ages I am highly interested in the do ut des-aspects of the relation between religious houses and the lay world. Key words here are: property, power, patronage and the role of religious institutions in the 'salvation…

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

Abdessamad El Amraoui defended his thesis on 6 Mai 2015.

PhD Defence

How are digital risk-profiles developed and used in practice?

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

PhD Defence

PhD Defence

PhD Defence

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

Conference