Peptides are routinely synthesized in the range of 5-80 amino acids, in an amount of 1-200 µmol (smaller and larger amounts are also possible).

Kros

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

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

Oxidation is a common degradation pathway that affects therapeutic proteins and peptides during production, purification, formulation, transportation, storage and handling of solid and liquid preparations. In the present work we review the scientific literature about structural and biological consequences…

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: 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.

Can the venom of snakes, scorpions and other animals be sources of new antibiotics?

Can cyclic peptides provide a new generation of antibiotics?

Promotores: Wim Jiskoot; Ferry Ossendorp

Bet v1, the major allergen in birch pollen, is one of the main causes of allergies such as asthma and rhino-conjunctivitis. Additionally it is the main cause of birch pollen allergy in humans.

PhD Defence

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.

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

It is estimated that approximately 30% of all proteins require a metal to function. Investigating the relationship between metal-binding and peptide/protein folding allows us to uncover fundamental rules for creating metallo-peptides and proteins, which in turn leads to the creation of new structures,…

Promotoren: G.F.A. Kersten, W. Jiskoot, Co-promotor: J-P. Amorij

Cationic peptide amphiphile nanoparticles are employed for co-delivery of immune modulator CpG and antigen. This results in better targeting to the antigen presenting cells and eliciting strong Th1 response, which is effective against the intracellular pathogens.

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

For effective cancer immunotherapy by vaccination, co-delivery of tumour antigens and adjuvants to dendritic cells and subsequent activation of antigen-specific cytotoxic T cells (CTLs) is crucial. In this study, a synthetic long peptide (SLP) harbouring the model CTL epitope SIINFEKL was encapsulated…

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

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

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.

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.

Influenza CD8(+) T-cell epitopes are conserved amongst influenza strains and can be recognized by influenza-specific cytotoxic T-cells (CTLs), which can rapidly clear infected cells. An influenza peptide vaccine that elicits these CTLs would therefore be an alternative to current influenza vaccines,…

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.

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 potential of liposomal cancer vaccines

Promotor: Prof.dr. E.J.J. Groenen

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

The GMP Facility facilitates development and production of Advanced Therapy Medicinal Products (ATMPs) and chemical (peptide) synthesis.

Liposomes hold great promise for peptide-based personalized cancer vaccination, especially when administered intradermally. However, current liposome preparation methods are very time consuming (resulting in long development times per formulation), whereas personalized cancer vaccination requires very…

Chapter 2 describes a post-synthetic methodology to introduce a fluorescent label in highly lipophilic, Pam3Cys based conjugates.

In the hunt for a vaccine against cervical cancer, fundamental knowledge about the immune system and organic chemistry have been brought together and have already resulted in a vaccine that is now being tested in clinical trials. Scientists are now working hard on an improved variant.

Seasonal influenza vaccines provide protection against matching influenza A virus (IAV) strains mainly through the induction of neutralizing serum IgG antibodies. However, these antibodies fail to confer a protective effect against mismatched IAV. This lack of efficacy against heterologous influenza…

Promotor: A. Kros, Co-promotor: R.R.C.L. Olsthoorn

Promotores: W. Jiskoot, F. Ossendorp

Macromolecular Biochemistry is a section of the Leiden Institute of Chemistry at Leiden University, comprising the PIs Marcellus Ubbink, Remus Dame, Aimee Boyle and Lars Jeuken.

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.

Promotor: Prof.dr. J.P. Abrahams

Alexander Kros studies supramolecular systems in a biological environment. The unifying theme between the projects in my lab is specific molecular recognition, i.e. the intermolecular interaction between complementary molecules with high affinity and selectivity. Studying, imitating and dissecting processes…

Lecture

Antibiotics are a class of medicine most people take for granted. But pathogenic bacteria are becoming more and more resistant to our antibiotics, and this poses a great challenge for future treatments. There is thus a great societal need to identify new molecules that can address new targets and be…

Synthetic hydrogels that mimic the natural extracellular matrix in the biophysical and biochemical cues it provides to cells are in high demand, however the cell phenotypes as they are observed in vivo in numerous cases have yet to be attained.

A new biophysical technique enables scientists to study the behavior of Aβ-peptide. This protein is known to play a role in Alzheimer’s, but for effective medication we need to know exactly what it does. Publication in Journal of Biological Physics on March 16th.

The goal of hit discovery is to identify suitable chemical starting points to modulate a drug target. A hit can be, a.o., a small molecule, a protein or mRNA. Hit identification is performed via rational design, genome mining, (targeted) library screening, or in silico approaches.

PhD Defence