The present thesis focuses on the pharmacological concept of drug-target interaction, which dates back to the beginning of modern pharmacology.

Promotor: A.P. IJzerman

Promotor: A.P. IJzerman

Over several decades, a variety of computational methods for drug discovery have been proposed and applied in practice. With the accumulation of data and the development of machine learning methods, computational drug design methods have gradually shifted to a new paradigm, i.e. deep learning methods…

G protein-coupled receptors (GPCRs), one of the largest families of membrane proteins, are responsive to a diverse set of physiological endogenous ligands including hormones and neurotransmitters.

This thesis explores different avenues to develop insurmountable antagonists for CC Chemokine Receptors, such as CCR1, CCR2 and CCR5.

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

Promotor: A.P. IJzerman Co-promotor: L.H. Heitman

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 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…

Promotores: A.P. IJzerman, H.W.T. van Vlijmen

Promotor: A.P. IJzerman

Promotor: Prof.dr. M. Ubbink

Promotores: H.S. Overkleeft, G.A. van der Marel, Co-Promotor: R.G. Boot

In this thesis, the focus lies on studying glucocorticoid receptor dynamics in living cells with the aim of understanding how this transcription factor finds its DNA target sites to regulate transcription.

This thesis describes the importance of being able to control the selectivity of potential drug candidates.

During the course of drug discovery translational steps are made.

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

Promotie

Promotor: H.P. Spaink, A.H. Meijer Co-promotor: R. Marin-Juez

Informatie over de de G. Rozenberg Research Award van het Leiden Institute of Advanced Computer Science (LIACS) is beschikbaar in het Engels.

Promotie

The function of TLRs in innate immunity has aroused worldwide attention soon after its discovery. Because of the broad functions of TLR2 in innate immunity, the drive for the development of TLR2-targeted vaccines or therapeutic treatments has accelerated in the last decades.

Promotie

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

Solute carrier (SLC) transporters are a large and diverse class of relatively understudied transmembrane proteins.

The work described in this dissertation contributes to a better mechanistic understanding of nanoparticles in vivo. To achieve that goal, we used the zebrafish as a highly predictive pre-screening model of nanoparticles.

Medicijnen werken niet volgens het ‘one size fits all’-principe, omdat genetische verschillen hun effectiviteit beïnvloeden. Dat blijkt uit innovatief onderzoek van promovendus Julia Hillger. Zij promoveert donderdag 7 december op haar proefschrift Take it Personal.

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.

HDL staat bekend als het ‘goede cholesterol’: het verlaagt de kans op hart- en vaatziekten. Sommige families hebben van nature veel HDL in het bloed. Onderzoek naar hun erfelijk materiaal kan bijdragen aan de ontwikkeling van nieuwe medicijnen die HDL verhogen.

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

Promotor: H.P. Spaink, Co-Promotor: A.H. Meijer

Hoogleraar Farmacochemie Ad IJzerman heeft de Nauta Award gewonnen voor zijn jarenlange onderzoek naar signaalverwerkende eiwitten die interessant zijn voor de ontwikkeling van nieuwe medicijnen: G protein-coupled receptors. De prijs wordt elke twee jaar uitgereikt voor verdiensten in de farmacochemie…

Source: Structure , Volume 22, Issue 8, pp. 1120-1139 (2014)

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

Adenosine is an endogenous ligand which exerts its action by activating adenosine receptors (ARs), while its circulating levels are controlled via a variety of mechanism and proteins, amongst others the equilibrative nucleoside transporters (ENTs).

The research described in this thesis shows that hypercholesterolemia, a well-established risk factor for atherosclerosis, can impact skin lipid pool and barrier function already at young age. In the field of atherosclerosis, we showed that the small peptide Lyp-1 can be used as a targeting molecule…

Description of Biotic ligand models: making an inventory of available models & assessment of the variability of the predicted HC5 using the BLMs in different Dutch water types (2005 - 2007)

Nog nooit was een kristalstructuur van een menselijk eiwitmolecuul in een celwand zo kristalhelder. De Leidse onderzoekers Ad IJzerman en Laura Heitman maakten samen met Amerikaanse collega’s de meest gedetailleerde kristalstructuur ooit van een doeleiwit voor geneesmiddelen. De onderzoekers publiceerden…

Promotie

Per 1 november is Laura Heitman benoemd tot hoogleraar Moleculaire farmacologie bij het Leiden Academic Centre for Drug Research (LACDR). Heitman draagt bij aan de ontdekking van nieuwe geneesmiddelen door onderzoek naar de interactie tussen medicijnen en hun aangrijppunt in het lichaam. ’Mijn uiteindelijke…

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.

This thesis focuses on the role of chemokine receptors CXCR3 and CCR2 in the inflammatory process and infection control using the zebrafish model.