Promotor: G.A. van der Marel, Co-Promotor: J.D.C. Codée

Design and synthesis of two 3-substituted swainsonine derivatives with the aim to improve the potency and selectivity towards Golgi alpha-mannosidase II.

This thesis has described novel synthetic methods to produce a variety of (glyco)peptides and their application in the study of various immunological processes.

Promotor: E.F.A. Deprettere, Co-Promotor: A.C.J. Kienhuis

By Marieke Liem and Frans Koenraadt. Domestic homicide constitutes an extreme type of interpersonal violence. This book offers a much-needed synthesis of the literature on domestic homicide, covering its history; the theories supporting it; its various forms such as filicide, intimate partner homicide,…

Cholesterol influences many pathways, including serving as precursor for adrenal steroidogenesis. Imbalance of cholesterol levels has been implicated in several diseases including cardiovascular diseases and its underlying pathology, atherosclerosis.

This Thesis focuses on the design and synthesis of ADP-ribosylated compounds that can be applied in biological studies.

Promotor: Prof.dr. A.P. IJzerman, Co-Promotor: L.H. Heitman

Adenosine diphosphate ribosylation (ADP-ribosylation) is a fascinating post-translational modification (PTM) that plays a role in a variety of cellular processes and is associated with several diseases, including cancer and viral infections.

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

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

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

The polypept(o)ide hybrid material attracted more and more attention over the past decade by combining the multifunctional characteristics of polypeptides with the shielding characteristics of polypeptoid-pSar possessing similar properties as a shielding material as polvethylene glycol(PEG). Polysarcosine…

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…

A full overview of MCBIM PhD theses.

This thesis describes the synthesis, analysis of various tetrazine bearing compounds and use in bioorthogonal chemistry.

In a typical glycosylation reaction, a donor is activated to form a (variety of) electrophilic species which can react with a nucleophilic acceptor, following a reaction mechanism having both SN1 and SN2 character.

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

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…

In this thesis the combinatorial use of bioorthogonal labelling and Electron Microscopy (EM)-based imaging techniques is explored to enable observations of specific molecular targets in their ultrastructural context within the cell.

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

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

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

Pseudomonas Aeruginosa is a Gram-negative bacterium which can form biofilms, increasing its resistance against antibiotics and the host immune system. Polysaccharides are an integral part of this biofilm, one of these polysaccharides is called Psl. PslG is a glycosidase, able to cleave this polysaccharide,…

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

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.

How do protein modifications work together to repair DNA, and what can we learn about these interactions to better understand disease?

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

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

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.

The glycosylation reaction is a pivotal reaction in creating new and complex oligosaccharides.

This thesis systematically studies the physicochemical properties of non-planar, propeller-shaped, polycyclic aromatic hydrocarbons. The synthesis of several so-called propellerenes is described on a gram scale, using optimized procedures aimed at using less hazardous reagents and reducing the amount…

Cytotoxic T-cells (CTLs) are involved in the clearance of viruses and killing of tumor cells.

Contact Bio-organic Synthesis

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…

Promotors: Prof.dr. E. Bouwman, Prof.dr. E. Drent

This thesis focuses on the synthesis, characterization and performance towards CO2 electroreduction of mono and bi-metallic particles based on p-block metals

MHC class I and MHC class II molecules present peptides to the immune system to drive proper T cell responses. Pharmacological modulation of T-cell responses can offer treatment options for a range of immune-related diseases.

Lecture

How can efficient chemical synthesis and clinical microbiology be combined to identify new antibiotics against Clostridioides difficile infections?

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…

Utilizing the polymeric platform of polypept(o)ides, this thesis describes synthesis and investigation of novel triblock copolymers to obtain carrier systems with multiple compartments for efficient siRNA delivery. Although the individual microstructure of nanoparticles differs depending on the polymeric…

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

This thesis describes the use of bioorthogonal proteins in immunological settings. It provides an introduction towards the field of protein modification, which was used throughout the thesis for the expression of proteins containing unnatural amino acids.