The channel through which two cell components exchange material appears to form at the edge of their contact surface, and not in the middle. This was discovered by the Leiden physical chemists Jelger Risselada and Edgar Blokhuis together with researchers from the University of Lausanne in Switzerland.…

With great sadness we share the news that Prof. Harold Linnartz passed away suddenly and unexpectedly on Sunday 31 December 2023. We are all in shock, and our thoughts are with his wife and children, other family, and friends. Harold was at the heart of our institute, as a researcher, as a supervisor,…

Since May, Assistant professor BioTherapeutics Lu Su works in our faculty. Although she is still young, she already worked in many different fields and co-operated on two publications in big scientific journals. How did she become so successful and what motivates her to keep researching the possibilities…

The goal of the research presented in this thesis was to explore the chemical space of ruthenium(II) photocages, investigate their ability to host potent chemotherapy drugs, and to red shift the activation wavelength of the most promising PACT candidates to conduct biological studies.

Cardiovascular diseases (CVDs) are the leading global cause of mortality. Endothelial dysfunction, an early reversible stage of CVD development, is marked by decreased nitric oxide production linked to Ca2+ influx in endothelial cells.

As leading cause of death worldwide, cancer is responsible for nearly 10 million deaths in 2020 according to World Health Organization (WHO). Cisplatin and its derivatives are commonly used chemotherapy agents for current cancer treatment in the clinics.

Microscopic insight on lipid-based nanomedicine in vivo remains limited to the perception of the knowledge that could be obtained: if we interpret only what we see, then we only believe to know. Although believing to know encapsulates an undefined amount of uncertainty in the exploration of lipid-based…

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

Bacteria often experience external challenges, such as changes in environmental conditions or attacks by bacteriophages.

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

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

Phosphorylation affects all four major biomolecules – proteins, lipids, carbohydrates and nucleic acids – and plays a pivotal role in the most fundamental cellular functions.

The Leiden Academic Centre for Drug Research (LACDR) is responsible for the research and education in Bio-Pharmaceutical Sciences carried out at Leiden University.

Overkleeft

The drug BIA 10-2474 inhibits fatty acid amide hydrolase (FAAH), a lipase that degrades a specific endocannabinoid. On the basis of this activity, BIA 10-2474 was being developed as a potential treatment for anxiety and pain. In a phase 1 trial of the drug, one subject died, and four others suffered…

A high-end label: Cyclophellitol aziridine-type activity-based probes allow for ultra-sensitive visualization of mammalian β-glucosidases (GBA1, GBA2, GBA3, and LPH) as well as several non-mammalian β-glucosidases (see picture). These probes offer new ways to study β-exoglucosidases, and configurational…

Three at the same time: a ligation strategy combining tetrazine–norbornene cycloaddition, Staudinger–Bertozzi ligation, and copper(I)-catalyzed click reaction was used to label the three catalytic activities of the proteasome simultaneously in a single experiment. The orthogonality of the three ligation…

Hydrodesulfurization (HDS) is an ubiquitous part of oil refining that ensures that fuels are cleaned of impurities and environment release of pollutants such as SOx and NOx gasses are minimized.

On the occasion of the Women & Girls in Science Day, BBC Science Focus Magazine highlighted 6 prominent female chemists. Among them is Leiden professor Ewine van Dishoeck: 'Astrochemist investigating the building blocks of life'.

This thesis highlights the significant role of surface geometry and oxidation state in determining CO adsorption behavior on copper surfaces.

The work in this thesis demonstrates how to obtain an atomic-scale picture of a diverse set of complex surface structures observed using STM, under disparate conditions.

Promotor: M.T.M. Koper, Co-promotor: L. Juurlink

Promotor: M.T.M. Koper, Co-promotors: A.I. Yanson, L.B.F. Juurlink

Promotor: M.T.M. Koper, Co-promotor: J.B.F. Juurlink

Promotor: M.T.M. Koper, Co-Promotor: L.B.F. Juurlink

The research presented in this thesis makes use of small molecules (as H2 , D2 and O2 ) on well-defined single crystal surfaces (flat Pt(111), flat Cu(211) and curved Pt(111)) to elucidate the role of surface structure and degrees of freedom in the reactant in specific surface reactions.

In this thesis, we study different curved single crystals because of the diversity of surface structures across their curvature.

Carbon dioxide capture and utilization technologies are necessary to create a truly circular economy. The electrochemical reduction of carbon dioxide to formate is an appealing carbon utilization method as it can be performed at room temperature and pressure, it only requires two electrons, and it has…

In this dissertation iron-based homogeneous catalysts were synthesized, characterized and investigated for water oxidation activity.

Climate change is a challenge for both current and future generations. New biological resources have to be developed in order to meet the demand for energy as well as the demand for food.

Before the large scale use of renewable energy sources can be implemented in our society, the storage of electrical energy needs to be tackled. Storage the energy as hydrogen via the reduction of protons is a good option.

Promotor: H.J.M. de Groot, Co-Promotor: A. Alia

Promotor: H.J.M. de Groot, Co-Promotor: A. Alia

Promotor: Huub J.M. de Groot, Co-promotor: Francesco Buda

Decentralized plug and play systems for energy production are the future picture of our society. Artificial photosynthetic systems are used for this purpose.

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

The main subject of this thesis is the design and synthesis of paramagnetic molecules for protein studies with NMR and EPR spectroscopy.

A key step in the synthesis of oligosaccharides and glycoconjugates is the formation of the glycosidic bond.

This dissertation explores new chemical strategies for the synthesis of self-adjuvanting peptide conjugates and immunomodulatory ligands aimed at targeted activation of the immune system.

Bet v1, the major allergen in birch pollen, is one of the main causes of allergies such as asthma and rhino-conjunctivitis. Additionally it is the main cause of birch pollen allergy in humans.

Due to the modern techniques of combinatorial chemistry and high-throughput screening, data on the biological activity of many millions of compounds is known. However, it is still very difficult to transfer this data into knowledge: if we know that compounds A and B bind to a certain protein with high…

The thesis describes the development, synthesis and biological evaluation of several proteasome inhibitor designs. Mainly, this work focusses on designing proteasome inhibitors that selectively inhibit the immunoproteasome, while leaving the constitutive proteasome mostly, if not completely, untouch…

This thesis describes the design and synthesis of novel small molecules based on sulfur-containing heterocycles for the inhibition of glycosidases and glycosyltransferases related to Fabry and Pompe disease.

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…

A deceptively simple, complicated paper

The aim of the research described in this thesis was to use structure-based design to optimise multiple properties of aryl sulfoxide monoacylglycerol lipase inhibitors as anti-inflammatory analgesics.

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

β-Lactamases are enzymes that can break down β-lactam substrates, such as antibiotics, preventing the use of these antibiotics for the treatment of various infectious diseases. However, some compounds, β-lactamase inhibitors, can block these enzymes allowing for possible treatments using a combination…