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, Co-Promotor: B.I. Florea

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.

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

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

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…

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

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…

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…

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

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.

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

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

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

To get a feeling of how we operate at LED3 when it comes to Early Drug Discovery, please browse through our case studies. When you select a case study you’ll find relevant contacts.

How do you ensure that a drug has an effect on the right protein – and nothing else? Chemist Anthe Janssen explored various methods for determining the selectivity of potential medicines. He also looked at the substance BIA 10-2474, after a man died in a French clinical trial in 2016. PhD defence on…

The goal of hit and lead optimization is to optimize suitable chemical starting points that can modulate a drug target. The methods and technologies used are similar to those in Hit Discovery, but once the compound has shown activity in an animal model, it moves from 'hit' to 'lead.'

Endocannabinoids - the body's own marijuana - are promising departure points for drug research. Professor of Molecular Physiology Mario van der Stelt examines whether inhibiting their production can be a way to fight inflammatory brain disease and to combat obesity. Inaugural lecture 19 October.

A European consortium has provided a disruptive technological breakthrough to allow the discovery and characterization of novel enzymes for industrial biotechnology. The technology will open the way to more efficient industrial processes such as in the biofuel, animal feed and paper and pulp industr…

Lecture

PhD defence