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.

The Novel chemical modalities research group is headed by Assistant Professor Sebastian Pomplun. Sebastian started at the division of Medicinal Chemistry within the LACDR in September 2021. His lab develops technologies for the discovery of novel chemical modalities that can address challenging drug…

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…

Overkleeft

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…

This thesis describes the development and optimization of the first molecular tools to study the enzyme PLA2G4E.

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

How can the Safe and Sustainable by Design (SSbD) framework developed in the SSbD4CheM project facilitate the creation of safer and more sustainable chemicals and materials across various industries?

Lecture

Developing new medicines is one of modern science's most significant hurdles, a process marked by high costs, long timelines, and frequent failures of promising candidates.

The inverse electron demand Diels-Alder (IEDDA) pyridazine elimination emerged in 2013 as a new bioorthogonal reaction and constitutes a prime example of what is now known as dissociative bioorthogonal chemistry. The research described in this Thesis aims to develop synthetic strategies which enable…

At the moment, over 350.000 chemicals are registered worldwide for production and use. Their application, however, may harm human health and the environment.

Chemical-induced organ toxicity is a major concern in the development and use of chemicals, including drugs, pesticides, industrial chemicals and cosmetics. In the last decades, the onset and progression of chemical-induced organ toxicity has been linked amongst others to perturbation of mitochondri…

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…

This thesis has described novel synthetic methods to produce a variety of (glyco)peptides and their application in the study of various immunological processes.

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

Kinase inhibitors are key therapeutic agents, particularly in oncology, yet their clinical efficacy is often hampered by off-target effects and limited understanding of their cellular target profiles.

How do chemical contaminants traverse and affect terrestrial biodiversity and ecosystems?

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

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

The research described in this thesis centered on retaining exo-β-glucosidases implicated in health and disease, in particular the human inherited lysosomal storage disorder, Gaucher disease (GD).

We review the state-of-the-art in the theory of dissociative chemisorption (DC) of small gas phase molecules on metal surfaces, which is important to modeling heterogeneous catalysis for practical reasons, and for achieving an understanding of the wealth of experimental information that exists for this…

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.

Neurodegenerative diseases pose a large medical and societal challenge. The etiology of these diseases is still poorly understood, which makes drug discovery for these diseases difficult.

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

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

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.

The work described in this Thesis is focused on the assembly of oligosaccharide fragments derived from a fungal polysaccharide, galactosaminogalactan (GAG) and fragments of the exopolysaccharide Pel, generated by Pseudomonas aeruginosa.

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…

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

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.

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?

Lecture

The endocannabinoid receptors CB1R and CB2R are involved in a plethora of processes, and consequently are involved in many pathological conditions. Their wide distribution makes the CBRs both an interesting therapeutic target and hard to study.

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

The focus of the described research in this thesis is on the oxidative stress response (Nrf2 pathway). The aim of the research presented in this thesis is to obtain more information concerning microRNAs which are involved in the Nrf2 pathway, to determine and evaluate the application of microRNAs for…

Antibiotic-resistant bacteria pose a major health threat. Addressing this challenge requires among others the development of new antibacterial compounds. The research described in this thesis focuses on discovering novel antibiotics from soil bacteria, specifically Streptomyces and Paenibacillus.Despite…

Thesis focused on uncovering the underlying mechanisms of the lysosomal storage disorders Gaucher's disease using chemical tools, biochemical assays and lipidomics.

The upscaling of Life Cycle Assessment (LCA) data is recognized as one of the main challenges in the ex-ante LCA of emerging technologies. This challenge arises since industrial-scale system specifications for these technologies are unknown and industrial data is lacking.

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

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

The ongoing increase in antimicrobial resistance combined with the low discovery of novel antibiotics is a serious threat to our health care.

This thesis focusses on the temperature structure in protoplanetary disks. The relation between structures seen in the dust and gas-phase molecules is investigated.

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.

Despite the history of studies on methanol formation from CO2, the dominant elementary reaction steps that constitute the chemical mechanism for this catalyzed process are not determined.

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.

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.