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.

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…

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

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

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.

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.

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

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.

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.

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.

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.

Overkleeft

Describe and identify what dosimetry parameters are of importance to interpret dose-response relationships (eg., mortality, sub-lethal, growth or reproduction inhabitation, DNA damage and reactive oxygen species, etc. ) for metal-based nanoparticles? How to develop quantitative models that enable to…

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

De Young Academy Leiden (YAL) heeft een 444 Interdisciplinary Activity Grant toegekend aan Anna van Duijvenvoorde en Stephanie Rap voor het organiseren van een seminar op het gebied van jongvolwassenen, neurowetenschappen en het recht.

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…

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

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

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

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

How presence, abundance and enzymatic activities of AM and EM fungi differently affect soil carbon sequestration processes?

The chemical synthesis of inhibitors and probes targeting endo-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…

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

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.

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.

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

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…

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

How soil microbial composition impacts structure and composition of the aboveground plant and animal communities?

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.

The work described in this thesis focuses on the development of linear or cyclized peptide probes against protein N-methyltransferases to characterize their specific binding behavior, providing further binding details for inhibitory activity study.

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.

Promotie

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…

The research aims to explore the evolutionary adaptability of enzymes and the impact of temperature on protein evolution pathways, using M. tuberculosis β-lactamase BlaC as the object of study. Enzymes inherently embody a delicate balance between activity and stability, and the acquisition of new enzymatic…

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

Monoacylglycerol lipase (MAGL) is the principal enzyme responsible for hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL inhibition provides several potential therapeutic opportunities, including anti-nociceptive, anti-inflammatory and anti-cancer activity.