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.

Het chemische biologie-onderzoek bij het Leids Instituut voor Chemisch Onderzoek (LIC) is gericht op het begrijpen van biologische processen op moleculair niveau, om zo onze kennis te vergroten over gezondheid en ziekte van de mens.

Overkleeft

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

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

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.

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.

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

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

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).

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

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.

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

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.

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

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: H.S. Overkleeft, G.A. van der Marel, Co-Promotor: R.G. Boot

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

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

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.

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…

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…

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.

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

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

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

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

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.

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.

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.

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

Glycoside hydrolases (glycosidases/GHs) are widely abundant enzymes in all kingdoms of life and are important biocatalysts that catalyze the hydrolysis of glycosidic linkages in oligo/polysaccharides, glycoproteins and glycolipids with tremendous efficiency

The increasing resistance of pathogenic bacteria to antibiotics necessitates the discovery of new medicines.

Global healthcare is on the verge of an antibiotic availability crisis as bacteria have evolved resistance to nearly all known antibacterials. Identifying new antibiotics that operate via novel modes-of-action is therefore of high priority.

Plant exudates appeared long time ago in the history line of life in the early Devonian. They are typical saps produced by specialized cells.

Glycosidases (GHs) are enzymes responsible for the degradation of carbohydrates and play many roles in human health and pathophysiology. Often, abnormal levels of glycosidase activity are markedly linked to human pathologies.

Thomas Bakkum en Tom van der Wel, promovendi bij het Leids Instituut voor Chemisch Onderzoek, winnen poster awards bij de EMBL Chemical Biology Conference 2018 in Heidelberg.

Wij richten ons op natuurlijke producten van onderzoek, de traditionele geneeskunde, etnobotanie en fytochemie.

Carbohydrates, alongside proteins and nucleic acids, constitute a crucial and versatile family of biomolecules present in all life forms. They manifest as monosaccharides, oligosaccharides, and polysaccharides, covalently bonded to proteins and fats. Carbohydrates are integral to plant and arthropod…

De uitgeverij American Chemical Society’s Publication Division (ACS) en de Nederlandse universiteiten, verenigd in de VSNU, hebben een akkoord bereikt om open access publiceren op te nemen als onderdeel van het uitgeverscontract. Vanaf 2017 worden alle nieuwe artikelen die een auteur, verbonden aan…

Promotor: Prof.dr.ir. J.G.E.M. Fraaije, Co-promotor: A. Kros

Catalysis is of extreme relevance in the production of everyday materials and plays a central role in many aspects of our life.

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

A difficulty of studies on chemical kinetics are the reaction time scales and detection of their intermediates.