Promotor: Prof.dr. H.S. Overkleeft

Lysosomal acid glucosylceramidase (GBA1) is a lysosomal enzyme that degrades glucolipids with its main substrate being glucosylceramide (GlcCer). Defects in the GBA1 gene lead to glycosphingolipidosis Gaucher disease (GD), in which the hydrolysis of GlcCer is impaired and therefore, it accumulates in…

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

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

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

Glycosidases are important enzymes in the turnover of polysaccharides and glycoconjugates, and are involved in a range of human pathologies including genetic disorders such as Gaucher and Pompe disease, but also in various cancers.

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.

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

De verhoogde activatie van het striatum, die adolescenten laten zien bij beloning, wordt meestal in verband gebracht met risicogedrag en negatieve gezondheidseffecten. In dit artikel in Nature Communications wordt een mogelijke positieve kant van die verhoogde activatie onderzocht. De activatiepiek…

Glycosidases are essential in fundamental biological processes and are responsible for the degradation of most (oligo)saccharides, glycolipids and glycoproteins.

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

Lysosomal glycosidases are acid hydrolases that fragment glycoconjugates in lysosomes.

This thesis provides an overview of the development of the Pair Configuration to Molecular Activity Coefficient (PAC-MAC) model.

Actinobacteria are well known for the production of bioactive natural products, many of which have applications in the fields of human, animal and plant health. Subject of this thesis are the anthracyclines, glycosylated aromatic polyketides with potent anticancer activity.

Phospholipase A/acyltransferase 3 (PLAAT3) and PLAAT4 are enzymes involved in the synthesis of bioactive lipids. Despite sequential and structural similarities, the two enzymes differ in activity and specificity.

Climate change is one of the largest challenges faced by humanity. To combat this research into alternatives to fossil fuels is ongoing. Dihydrogen is considered a good alternative fuel, since its burning only forms water.

This thesis describes research aimed at discovering inhibitors selective for either of the two endoplasmic reticulum α-glucosidases, ER-I and ER-II, with the overarching goal of discovering new antiviral agents to treat viruses that rely on host N-glycosylation for proliferation.

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

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.

Een belangrijke uitdaging in de neurowetenschappen is het begrijpen hoe neuronen in honderden onderling verbonden hersengebieden sensorische input integreren met eerdere verwachtingen om bewegingen te initiëren en beslissingen te nemen.

The research described in this thesis focused on the preparation of S/N functionalized carbene ligands and their transition metal complexes, and the exploration of their application as electrocatalysts for proton reduction.

Plant architecture has distinct forms in different plant species, but also within a species the finalarchitecture of a plant is determined by its gradual development and changes therein induced by environmental conditions during the plant’s life cycle.

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

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

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

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).

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

Alex Brandsen en Wouter Verschoof-van der Vaart, promovendi bij de onderzoeksgroep Digital Archaeology en het Data Science Research Programme, hebben een 444-beurs van de Young Academy Leiden ontvangen. Hiermee gaan ze in Oxford een sessie houden om de samenwerking te verbeteren tussen onderzoekers…

Promotor: Prof.dr. G.P. van Wezel

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

The chemical synthesis of inhibitors and probes targeting endo-glycosidases.

Neuraminidases are enzymes that cleave glycosidic linkages of sialic acid. These enzymes are involved in influenza infections as well as in many cellular processes in mammals and micro-organisms.

The recently introduced nature-originated deep eutectic solvents, so-called natural deep eutectic solvents (NADES) are considered as truly green solvents, which composed of natural ingredients found abundantly in organisms.

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

To this day, all cyclophellitol-based inhibitors and ABPs have been close analogues of their natural substrate counterparts. As a result, these probes showed high selectivity towards their target glycosidases.

This thesis describes the synthesis and biochemical evaluation of a variety of cyclophellitol based activity-based probes and inhibitors targeting various endo- and exo-acting retaining glycosidases. In the last two decades a variety of probes and inhibitors for (hemi)cellulose degrading enzymes have…

Less than 1 in 10 drug candidates that enter phase 1 clinical trials actually gets approved for human use.

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.

Catharanthus roseus (Madagascar periwinkle) produces valuable monoterpenoid indole alkaloids (MIAs) such as vincristine and vinblastine, crucial for cancer treatment.

CONCLUSION: This study demonstrates that human macrophages can be induced to exert direct anti-tumor activity against osteosarcoma cells. Our observation that the induction of macrophage anti-tumor activity by L-MTP-PE required IFN-gamma may be of relevance for the optimization of L-MTP-PE therapy in…

This thesis focuses on the design and synthesis of activity-based probes and inhibitors targeting enzymes involved in the degradation of specific plant glycans.

Prof.dr. J. Memelink

Polymyxins are clinically used antibiotics, discovered in mid-20th century. Once abandoned due to excessive nephrotoxicity, they are now used increasingly to address infections caused by multi-drug resistant Gram-negative bacteria.In this thesis, we describe the development and synthesis of analogues…

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

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

Gaucher disease is a rare metabolic disorder, in which a mutation of the enzyme glucocerebrosidase (GBA1) causes buildup of its substrate glucosylceramide and the deacylated counterpart glucosylsphingosine in lysosomes.

The research described in this thesis combines the latest insights in lysosomal function with lysosome centred cell signalling.

The confinement of molecular catalysts in metal-organic frameworks has the potential to lead to significant improvements in selectivity, long term activity and catalyst stability.

In 2019 bestond de Universiteit Leiden 444 jaar. Deze bijzondere leeftijd vroeg om een bijzondere viering, samen met de inwoners van Leiden en Den Haag. In, met en voor de stad.