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.

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.

Promotie

Within this thesis the central stage is taken by the discovery and investigation of transglycosylation of sterols. First, investigation focuses on the development of a method to accurately detect and quantify glucosylated metabolites in biological materials.

Several techniques are explored for going beyond the born-oppenheimer static surface model for molecule-surface reactions.

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.

Eiwitten uit het Golgi-complex van de cel op een gecontroleerde manier vernietigen. Dat is de focus van het baanbrekende onderzoek van chemicus Marta Artola. Door een nieuwe technologie te ontwikkelen gericht op specifieke eiwitten in het Golgi-complex, wil Artola nieuwe mogelijkheden voor medicijnontwikkeling…

Evolution acts via mutations in amino acid sequences. Substitution of essential amino acids leads to a nonfunctional protein. l.

Promotor: Prof.dr. M. Ubbink, Co-promotor: G. Siegal

This thesis presents pioneering work on the panchromatic emission of some of the most luminous galaxies in the early Universe: star forming galaxies and active galactic nuclei.

Animal diet studies are critical for understanding ecological processes such as trophic interactions, energy flow, and nutrient cycling. By examining what animals consume, ecologists gain insights into species specialization, predator-prey relationships, and ecosystem management.

Lezing

Leidse onderzoekers hebben een enzym ontdekt dat bacteriën helpt plastic af te breken én erop te groeien, een veelvoorkomend enzym dat mogelijk bijdraagt aan duurzamere plasticverwerking. De bevindingen zijn gepubliceerd in Nature Communications.

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

The primary goal of this research is to deepen our understanding of substrate-enzyme interactions in Glycoside hydrolases. For this purpose, Bacillus circulans xylanase (BcX) has been selected as a well-established model to examine the Michaelis complex and glycosyl-enzyme adduct.

The research presented in this thesis explores the chemotherapeutic potential of metal-based compounds as chemotherapy agents, with an initial focus on the synthesis and DNA interaction studies of platinum and palladium compounds utilizing the [Pt(bapbpy)]2+ scaffold. The study identifies intercalation…

The thesis focuses on synthesis strategies in oligosaccharide campaigns, and the influence of protecting groups.

Promotor: Prof.dr. M. Ubbink

Promotor: M. Ubbink, Co-Promotor: R. T. Dame

This thesis takes steps toward understanding the interaction between gas-phase and solid-state molecules in star- and planet-forming regions.

Promotor: Prof.dr. E. Bouwman, Co-promotor: S. Bonnet

In the search for sustainable energy solutions, the idea of artificial photosynthesis has been proposed as an approach with which to use water and sunlight to produce hydrogen.

Metals surfaces form a group of effective catalysts for the reaction of small molecules such as hydrogen (H2).

Promotor: J.W. van Holten

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…

Op 28 september bezocht de beroemde scheikundige Carolyn Bertozzi de Universiteit Leiden om te spreken tijdens de LED3 seminar. Precies één week later werd bekend dat zij de Nobelprijs voor Scheikunde zou ontvangen. De Leidse chemici Sebastian Pomplun en Hermen Overkleeft zijn fan: ‘Het is een hele…

This thesis investigates the structural evolution and assembly of galaxies since the first few billions years after the big bang.

Outflows are crucially important for the gas budget and evolution of luminous star-forming galaxies and AGNs, with observed mass outflow rates of the same order as the star formation rate. Greater star formation and black hole growth lead to more intense feedback and outflows, resulting in self-regulated…

With increasing carbon dioxide levels in the atmosphere and their detrimental effect on the global climate, modern society needs to push for more renewable energy sources. Storing widely accessible and abundant solar energy in chemical bonds in the form of molecular fuel via artificial photosynthesis…

Organic molecules in interstellar space are important as they influence the structure of galaxies and star formations. Studying catalytic processes in space allows us to understand how molecular species are formed and chemically evolved in the interstellar medium and solar system objects.

Studievoorlichting

Promotor: Prof.dr. M. Ubbink

Protein–protein complexes are formed via transient states called encounter complexes that greatly influence the formation of the stereospecific complex.

Every organisms in the tree of life faces the same challenge: the length of its DNA exceeds the volume of the cell it needs to fit in. Several strategies have evolved to solve this problem, one of them being the expression of proteins that bind and organize the DNA.

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).

The lysosomal β-glucosidase named glucocerebrosidase (GCase) is a retaining β-glucosidase that hydrolyzes the glycosphingolipid glucosylceramide (GlcCer) to ceramide and glucose at acid pH.

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…

Several single-stranded RNA viruses make use of Xrn1-resistant RNAs in their 3’ untranslated regions of their genome RNAs in order to increase their pathogenicity.

Nucleoid associated proteins maintain the architecture of the bacterial chromosome and regulate gene expression, hinting that their role as transcription factors may involve local three-dimensional chromosome re-modelling.

Advanced UHF MRI techniques provide powerful tools for studying the zebrafish brain, an emerging model in neurological research. In this work, various MRI and localized MRS methods are optimized and employed for UHF strength for studying the zebrafish brain.

Promotor: Jaap Brouwer, Co-promotor: Remus Th. Dame

Lysosomal glycosidases are acid hydrolases that fragment glycoconjugates in lysosomes.

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…

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We prove a p-adic version of the work by Gross and Zagier on the differences between singular moduli by proving a set of conjectures by Giampietro and Darmon, who investigated the factorisation of a rational invariant associated to a pair of CM-points on a genus zero Shimura curve, obtained as the ratio…