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

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

Synthetic methodlogy is described, aiding in the synthetic preparation of putative inhibitors of retaining and inverting glycosidases and glycosyl transferases. All constructs are cyclophellitol-based cyclitols.

Het proefschrift omschrijft de chemische synthese van fenolische glycolipiden van verschillende mycobacteriën met het doel om deze te kunnen gebruiken voor immunologisch onderzoek.

This thesis describes the development of a variety of mannosylated conjugates. Antigen presenting cells bear mannoside recognizing receptors that actively transport antigen into the cell. This thesis exploits this feature for the development of improved vaccines.

This Thesis describes the synthesis of D-alanylated ribitol-based wall teichoic acids from S. aureus to probe their interaction with immune-binding partners.

Sphingolipids are important membrane compounds with a variety of functions. In mammalian cells, different enzymes are involved in the metabolism of sphingolipids, but interruption of this metabolism process leads to different diseases.

Nicotinamide adenine dinucleotide (NAD+) is the substrate used for the introduction of the ubiquitous and highly dynamic PTM in which either one or multiple adenosine diphosphate ribose (ADPr) moieties are covalently attached to a nucleophilic side chain of an specific amino acid in the target protein…

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.

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

The research described in this Thesis was aimed at designing and synthesizing nature-inspired compounds as part of TB vaccine discovery.

Promotores: H.S. Overkleeft, G.A. van der Marel, Co-Promotor: J.D.C. Codee

Carbohydrates are present on the surface of bacteria making them suitable antigen candidates for vaccine development. This thesis deals with the synthesis of two carbohydrate-based components; the capsular polisaccharide of S. aureus type 5 and teichoic acids from staphilococci and enterococci speci…

Photocatalysis has emerged as a powerful tool for enabling challenging transformations in organic synthesis. This thesis explores the development of several photocatalytic reactions designed to form carbon-heteroatom bonds from less-functionalized precursors.

The work in this thesis has been focused on two subjects. The first is the assembly of alginate oligosaccharides and the generation of building blocks for the enzymatic synthesis of alginate, and the second is the total synthesis of large fragments of the zwitterionic SP1 polysaccharide.

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

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

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

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.

Carbohydrates, alongside proteins and nucleic acids, constitute a crucial and versatile family of biomolecules present in all life forms. They manifest as monosaccharides, oligosaccharides, and polysaccharides, covalently bonded to proteins and fats. Carbohydrates are integral to plant and arthropod…

This work has described synthetic strategies towards well-defined structures resembling capsular polysaccharide (CPS) fragments, CPS mimics, teichoic acid (TA) fragments as well as a third-generation ring-closing tandem metathesis (RCM) linker to better exploit the potential of automated synthesis.

Dit zijn de mensen die binnen de Universiteit Leiden actief zijn op het gebied van kunstmatige intelligentie.

Carbohydrates, or sugars, are the most diverse and most abundant biomolecules known. However, the isolation of carbohydrate samples in sufficient amounts and purity is often impractical or even impossible, so the chemical synthesis of glycosides becomes relevant. The glycosylation reaction, in which…

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

This dissertation presents the synthesis and evaluation of antibody recognition for various capsular polysaccharide (CP) fragments of Staphylococcus aureus (S. aureus).

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.

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

This Thesis describes a strategy to synthesize 1,2-cis-oligosaccharides modulated by additives, such as dimethylformamide (DMF), triphenylphosphine oxide (Ph3P=O) and N-methyl(phenyl)formamide (MPF), using building blocks that carry solely benzyl type protecting groups and are therefore of uniform r…

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,…

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

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.

This thesis describes the use of a combined approach of computational and experimental techniques to gain novel insights to understand the glycosylation reaction and its reactive intermediates.

Antibiotic resistance, caused by widespread use of antibiotics, leads to bacterial infections that are difficult, if not impossible, to treat and is a major worldwide health concern.

This thesis describes the design and synthesis of fragments of various cell wall carbohydrates of the Streptococcus species, including the branched Group B-specific antigen (GBC) of Group B Streptococcus, glycerol phosphate (GroP) modified group A carbohydrate (GAC), and the O-acetylated type 1 capsular…

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

Schistosomiasis is an acute and chronic disease caused by blood dwelling parasitic trematodes of the genus Schistosoma, and it is classified as the second most socioeconomically devastating parasitic disease, second only to malaria.

A key step in the synthesis of oligosaccharides and glycoconjugates is the formation of the glycosidic bond.

One of the main challenges in the development of an effective anti-cancer vaccine is the generation of an adequate and directed cellular immune response.

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

Glycoconjugate vaccines are composed of microbial poly- or oligosaccharides covalently linked to a carrier protein.

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…

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

Het Leids Instituut voor Chemisch Onderzoek (LIC) krijgt er met Sylvestre Bonnet, Jeroen Codée en Remus Dame maar liefst drie nieuwe hoogleraren bij. Bonnet wordt hoogleraar in de Bioanorganische Chemie, Codée hoogleraar in de Organische Chemie en Dame hoogleraar in de Moleculaire en Cellulaire Bioc…