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: Prof.dr.ir. J.G.E.M. Fraaije, Co-promotor: A. Kros

Cyclic peptides are investigated as a platform to induce different orientations between various ligands.

Viral diseases constitute one of the major challenges in modern medicine. Membrane-targeting have broad-spectrum potential and could distinguish viral membranes from the host cell plasma membrane by the difference in membrane curvature.

A structural investigation of coiled coil peptides used as membrane fusogens, mimicing naturally occuring coiled-coil fusion proteins. Synthetic modifications have been made to alter lipid attachment, secondary structure and to insert photoactive azobenzene moieties for active control over coiled coil…

Membrane fusion is a vital process in living organisms and is mediated by zipper-like proteins.

Promotor: Prof.dr. J.G.E.M. Fraaije, Co-promotor: A. Kros

Despite the fact that gold nanoparticles (GNPs) are one of the most studied nanoparticles, there is still a necessity for new approaches allowing for effective protective coating to enable wider use of GNPs in biomedical applications.

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.

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.

This thesis presents the first synthetic peptides ADP-ribosylated on serine, threonine, tyrosine, arginine and cysteine.

Peptiden worden routinematig gesynthetiseerd in het bereik van 5-80 aminozuren, in een hoeveelheid van 1-200 µmol (kleinere en grotere hoeveelheden zijn ook mogelijk).

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.

In deze opleiding, verzorgd door het Leiden Institute of Chemistry, zoek je naar oplossingen voor complexe, maatschappelijke problemen in volksgezondheid en milieuvraagstukken. We bieden op maat gemaakte, individuele studieprogramma’s, en je hebt de mogelijkheid om onderzoek te doen in het buitenland…

Promotores: Wim Jiskoot; Ferry Ossendorp

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

This thesis describes the design, synthesis, and immunological evaluation of varying (neo)antigenic peptide conjugates containing either a TLR2 or a TLR7 agonist.

The first steps are made in personalised cancer vaccination strategies, which aim to induce a more specific immune response with fewer side effects. The activation of cytotoxic T cells is crucial for an effective immune response.

This thesis is concerned with the constitution of chiral responsive matrix assemblies that may undergo light-driven conformational changes and self-select vibrations to develop vibronic states for driving semi-classical coherent transfer with nearly 100% yield in a lossless NCAP process.

Promotores: Prof.dr. G.F.A. Kersten, W. Jiskoot, Co-promotor: J-P. Amorij

If mankind wants to survive into the 22nd century, we will need to change the way we live drastically. The human impact on our planet is everywhere, we are changing the atmosphere, the oceans and the land, leading to global warming, climate change, loss of biodiversity and pervasive pollution. There…

The research described in this thesis focused on the use of bioorthogonal antigens to investigate immunological processes in antigen presenting cells. Bioorthogonal antigens are antigenic proteins produced through recombinant expression in a methionine auxotrophic E. coli strain.

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.

The ongoing increase in antimicrobial resistance combined with the low discovery of novel antibiotics is a serious threat to our health care.

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…

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

Plant-microbe interaction resulted in different physio/chemical responses by host plant and interacting rhizobacteria.

Biopolymer sequencing with graphene edge-based tunnel junctions has the potential to overcome current limitations with the third generation of sequencing based on biological nanopores.

Antibiotic-resistant bacteria pose a major health threat. Addressing this challenge requires among others the development of new antibacterial compounds. The research described in this thesis focuses on discovering novel antibiotics from soil bacteria, specifically Streptomyces and Paenibacillus.Despite…

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.

Laboratory, observation and modeling work on the dissociation of polycyclic aromatic hydrocarbons in interstellar environments and the formation of new molecular species through the fragmentation process.

Promotor: Prof.dr. J.G.E.M. Fraaije, Co-promotor: A. Kros

Large parts of the research described in this Thesis aims at the development of oligopeptide-masked toxins and their in situ immunoproteasome-mediated activation.

Promotor: J.G.E.M. Fraaije, Co-Promotor: A. Kros

In het schoolvak scheikunde is de concept-context benadering ingevoerd. Hans Vogelzang onderzocht of de Scrum-methodologie kan helpen bij het vormgeven van lessen met deze benadering.

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…

This dissertation contains four works during my PhD. Different biomaterials have been designed based on coiled-coil peptides. These biomaterials have a range of applications, inclusing drug delivery, cell sorting to cell-cell fusion.

This thesis introduces the concept of

Promotie

The aim of this thesis is to study cell-cell interactions and the development of an assay to explore and quantify the exchange of membrane compounds.

This thesis is largely an experimental study on the formation of solid-state simple and complex organic molecules in the H2O-rich and CO-rich ice phases of dense interstellar clouds and dark cores.

Multiple stars, that is two or more stars composing a gravitationally bound system, are common in the universe.

Promotor: J. Schaye

This thesis examines the link between simple molecules and the underlying structure and chemistry within protoplanetary disks - the birthplaces of planets.

The studies presented in the work show the potential of the integrative use of biophysical data in defining the structural basis of protein interactions.

The thesis describes the use of electron paramagnetic resonance (EPR) spectroscopy, in continuous wave and pulse modes, to address the interaction of α-Synuclein (αS) with membranes and the aggregation of αS.

Given the accelerating appearance of antimicrobial resistance, there is an urgent need for more fundamental research into novel antibiotic strategies. The work in this thesis helps to address this global problem by developing new antibiotic compounds, inspired by the antibacterial mechanisms of the…

Advanced mass spectrometry of glycosphingolipids takes the central stage in this thesis. Investigations focus on characterization of glycosphingolipid metabolism in health and disease with emphasis to the detection and accurate quantitation of known and so far unknown glycosphingolipids and closely…

With the rise of multi-drug resistant bacterial pathogens, the possibility of a post-antibiotic world is quickly becoming reality.

To address the fundamental questions of how life on Earth emerged and how common life may be in the Universe, it is crucial to know the chemical composition of the planet-forming material.