During the course of drug discovery translational steps are made.

The studies presented in the work show the potential of the integrative use of biophysical data in defining the structural basis of protein interactions.

The research in the Biosyn group is focused on the design, synthesis and function of the four major types of biomolecules: nucleic acids, carbohydrates, peptides and lipids and hybrid structures thereof. These biomolecules and their derivatives are used in drug discovery and chemical biology, to develop…

Synthetic hydrogels that mimic the natural extracellular matrix in the biophysical and biochemical cues it provides to cells are in high demand, however the cell phenotypes as they are observed in vivo in numerous cases have yet to be attained.

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…

Glycoconjugate vaccines are composed of microbial poly- or oligosaccharides covalently linked to a carrier protein.

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.

Self-assembly is an abundant process in nature and is vital to many processes in living organisms.

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

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

PhD defence

PhD defence

The molecular mechanisms that instigate a healthy cell to become malignant are fueled by (epi)genetic alterations in so-called driver genes.

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

Key publications of the Computational Drug Discovery group

In this thesis, a system pharmacology approach, integrating metabolomics, pharmacology and chemical biology, was applied to understand and modulate the endocannabinoid system across different model systems (cells, zebrafish, mice and humans).

The indane (2,3-dihydro-1H-indene) ring system is an attractive scaffold for biologically active compounds due to the combination of aromatic and aliphatic properties fused together in one rigid system.

An integrated approach for the simultaneous prediction of polypharmacology and binding affinity/potency of small molecules.

BlaC is the β-lactamase of Mycobacterium tuberculosis. We show that it can recover from inhibition by clavulanic acid and that phosphate helps it do so.

PhD defence

The Leiden Academic Centre for Drug Research (LACDR) received no less than three awards during the Figon Dutch Medicine Days. Bas Goulooze won the PhD Prize for best PhD candidate, Natalia Ortiz Zacarías and Huub Sijben both received a poster prize. ‘Scientists must be able to communicate their research…

While bioinformatics methods deal with the analysis of sequence information (be it proteins or DNA), the field of cheminformatics is concerned with the analysis of small-molecule datasets.

An overview of awards and prizes granted to our staff and students in 2018, as well as special appointments and royal distinctions.

PhD defence

PhD defence

PhD defence

PhD defence

Tackling key challenges of Chemical Biology and Medicinal Chemistry to aid drug discovery is one of the focus areas of Leiden University. To this end, the Leiden Early Drug Discovery & Development network (LED3) was established by the Leiden Institute of Chemistry (LIC), the Institute of Biology Leiden…

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…

The objective is to develop in vitro antigen degradation assays in order to mimic the fate of the antigen in vivo.

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.

This thesis describes the synthesis and biological evaluation of TLR2/6, TLR4, TLR7/8 and TLR9 ligands, of which the activity can be conditionally controlled.

Research projects

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

Natural product inspired antibiotics to address resistance

Medical Biochemistry is a section of the Leiden Institute of Chemistry at Leiden University. The section is headed by Prof. Dr. Hans Aerts.

Research question

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

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

PhD defence

PhD defence

Netherton Syndrome (NTS) is a rare genetic skin disease caused by mutations in the serine protease inhibitor Kazal-type 5 gene, which encodes the lympho-epithelial Kazal-type-related inhibitor. NTS patients have a profound impaired skin barrier function. Because SC lipids play a crucial role in the…

PhD defence

PhD defence

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.

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.

Supramolecular polymers are class of materials that are formed by non-covalent interactions such as hydrogen bonding, π-π interactions, electrostatic interactions and the hydrophobic effect.

Vancomycin is a last-resort antibiotic for the treatment of many Gram-positive bacterial infections, while remaining inactive against Gram-negative strains.