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

Transplantation of labial salivary glands to the eyelids for patients with dry eye appears to give excellent results clinically.

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…

The disease acute myeloid leukemia (AML) is characterized by fast progression and low survival rates.

Can a new proteomics workflow be developed to link genes and gene clusters to bioactive molecules, identify novel compounds and enhance the production in the Streptomyces lividans enzyme?

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.

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.

Overkleeft

The Leiden Institute of Chemistry is proud to offer the “Leiden Chemical Biology Lectures”. This lecture series aims to bring excellent researchers in the field of chemical biology to our university, and to expose our students to top science conducted in this area.

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

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…

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…

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

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

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

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.

How and why latex bearing plants select specific chemical compounds for eco-chemical interactions with its biotic factors?

In what way can new tools and techniques be used to develop drug candidates for the treatment of neurological disorders?

Overkleeft

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,…

How can we make make accurate predictions for reactions of molecules on metal surfaces?

This perspective addresses four challenges facing theorists whose aim is to make quantitatively accurate predictions for reactions of molecules on metal surfaces, and suggests ways of meeting these challenges, focusing on dissociative chemisorption reactions of H2, N2, and CH4.

MHC class I and MHC class II molecules present peptides to the immune system to drive proper T cell responses. Pharmacological modulation of T-cell responses can offer treatment options for a range of immune-related diseases.

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

Is it possible for sugar patterns on cells to activate the immune system to combat cancer?

Advanced sensing techniques require graphene with high quality and well-controlled surface chemistry.

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

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.

Sphingolipids are important membrane compounds with a variety of functions. In mammalian cells, different enzymes are involved in the metabolism of sphingolipids, but interruption of this metabolism process leads to different diseases.

Plants produce an astonishing variety of secondary metabolites (SMs) which are thought to play vital roles in the fitness of plants through ecological interactions.

This thesis describes the design and synthesis of fragments of various cell wall carbohydrates of the Streptococcus species, including the branched Group B-specific antigen (GBC) of Group B Streptococcus, glycerol phosphate (GroP) modified group A carbohydrate (GAC), and the O-acetylated type 1 capsular…

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

This paper describes two synthetic lipid models designed to replace human stratum corneum (SC) in studies of the impact of volatile organic chemicals on the molecular organization of the skin barrier lipids.

Walsh

Cellular stress response pathways are activated upon exposure to chemicals and help organisms deal with various molecular dangers (e.g. oxidative stress). When these pathways become hyper-activated an adverse response takes place and cells die, which may lead to organism-level toxicity such as drug-induced…

Promotor: E. F. van Dishoeck, Co-promotor: C. Walsh

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

Methods for accurately computing the interaction of molecules with metal surfaces are critical to understanding and thereby improving heterogeneous catalysis.

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

Promotor: Jelle S. Kaastra Co-promotor: Jelle de Plaa

How can we, together international experts, define future needs of R+D contributions for innovations in the field of risk-based management of chemicals and products in a global perspective using alternative testing strategies to minimize animal tests?

Promotor: P.G.L. Klinkhamer, Co-Promotores: K. Vrieling, P.P.J. Mulder

Aim of the proposal is to develop lugdunomycin into a drug candidate able to treat infectious diseases caused by multi-drug resistant pathogens.

The power of personalized nutrition lies in being able to conduct clinical research on healthy people while capturing metabolic markers sensitive to the impact of environmental and metabolic stressors (e.g. diet, changing sex hormones and the menstrual cycle).

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).