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,…

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

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…

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…

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.

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

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

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…

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

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

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…

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

The Protein Centre can supply you with purified proteins that are essential for many experiments, ranging from in vitro inhibitor screening and enzymatic analysis to manipulation of life cells.

Promotor: Prof.dr. E.J.J. Groenen

How can we develop a new microscope that can distinguish individual atoms in proteins?

Promotor: Prof.dr. C.A.M.J.J. van den Hondel, Dr. ir. V. Meyer, Co-promotor: Dr. A.F.J. Ram

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

Oxidation is a common degradation pathway that affects therapeutic proteins and peptides during production, purification, formulation, transportation, storage and handling of solid and liquid preparations. In the present work we review the scientific literature about structural and biological consequences…

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.

Promotor: M. Ubbink, Co-promotor: G. Siegal

Since its beginning, Leiden University has been one of Europe's leading international research-intensive universities.

Promotor: M. Ubbink, Co-promotor: G. Siegal

Supervisor: Anna Vlachodimou

PhD Defence

Supervisor: P.J.J. Hooykaas Co-Supervisor: R. Offringa

Promotor: W. Jiskoot, Co-promotor: A. Hawe

PhD Defence

PhD Defence

PhD Defence

Promotor: M. Ubbink, Co-promotor: G. Siegal

In our research protein translocation from Agrobacterium into yeast and plant cells is studied to obtain fundamental insights in the translocation process

Conference

In this study, we evaluated the influence of supercritical carbon dioxide (scCO2) spray drying conditions, in the absence of organic solvent, on the ability to produce dry protein/trehalose formulations at 1:10 and 1:4 (w/w) ratios.

The present thesis focuses on the pharmacological concept of drug-target interaction, which dates back to the beginning of modern pharmacology.

Hass

The RNA guided endonuclease based on the CRISPR/Cas system of Streptococcus pyogenus is a potent new tool for genome engineering in plants.

Source: Purinergic Signal., Volume 10, Issue 3, pp. 441-53 (2014)

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,…