The indane (2,3-dihydro-1H-indene) ring system is an attractive scaffold for biologically active compounds due to the combination of aromatic and aliphatic properties fused together in one rigid system.

PNAS publication on protein encounter complexes

Protein–protein complexes are formed via transient states called encounter complexes that greatly influence the formation of the stereospecific complex.

Monoacylglycerol lipase (MAGL) is the principal enzyme responsible for hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL inhibition provides several potential therapeutic opportunities, including anti-nociceptive, anti-inflammatory and anti-cancer activity.

The aim of the research presented in this thesis was to develop new methods forchallenging systems in liquid-state NMR using paramagnetic effects generated by thetwo-armed probe CLaNP-5.

Ice, the solid state of water, plays an important role on our planet as well as the entire universe.Despite the fact that an individual water molecule has a very simple structure, its chemical bonding in the solid phase can be surprisingly complex.

Human civilization consumes a huge amount of fossil fuels, which has resulted in an atmospheric CO2 level which has not been higher in over 800 millennia.

Promotor: Prof.dr. M. Ubbink

Despite the history of studies on methanol formation from CO2, the dominant elementary reaction steps that constitute the chemical mechanism for this catalyzed process are not determined.

Global healthcare is on the verge of an antibiotic availability crisis as bacteria have evolved resistance to nearly all known antibacterials. Identifying new antibiotics that operate via novel modes-of-action is therefore of high priority.

The main subject of this thesis is the design and synthesis of paramagnetic molecules for protein studies with NMR and EPR spectroscopy.

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.

Cambridge University Press has published a new book co-authored by researchers from Leiden University, offering both an introduction to machine learning and deep neural networks, and an overview of their applications in quantum physics and chemistry — from reinforcement learning for controlling quantum…

This thesis describes the development and optimization of the first molecular tools to study the enzyme PLA2G4E.

Promotor: J.P. Abrahams, Co-Promotor: N.S. Pannu

Leiden University has developed a radically different method for large scale production of diverse nanoparticles and their alloys.

Due to their central physiological roles in living organisms, retaining beta-glycosidases have been the subject of tremendous research efforts to examine their structure/function relation using numerous biophysical and biochemical approaches.

This thesis describes the structural and biochemical characterization of the β-lactamase BlaC from Mycobacterium tuberculosis (Mtb), and the Alr and YlmE proteins from Streptomyces coelicolor A3(2).Mtb is the main cause of tuberculosis.

In this thesis I highlight the applications of Oxford Nanopore Technologies (ONT) sequencing. This technique is a relatively new approach in the sequencing field, where nanopores are embedded in a membrane, DNA molecules are pulled through nanopores and an electrical current serving as the sequencing…

Marc Koper’s research focuses on electrocatalysis and electrochemical surface science for sustainable energy and chemistry. Reactions of interest are the redox reactions of the oxygen/hydrogen cycle (water oxidation, hydrogen evolution), the carbon cycle (reduction of carbon dioxide, oxidation of small…

Hydrocarbonylation of alkenes with carboxylic acids in synthesis of carboxylic acid anhydrides is relatively less explored. We herein present a study and optimization of a palladium-catalyzed hydrocarbonylation reaction of alkenes using carboxylic acids as the nucleophile, by which acid anhydrides can…

The Graduate School of Science offers PhD programmes spanning the entire spectrum of science from Mathematics to Environmental Science.

Promotor: Prof.dr. J.P. Abrahams, Prof.dr. M. van Heel

β-Lactamases are enzymes that can break down β-lactam substrates, such as antibiotics, preventing the use of these antibiotics for the treatment of various infectious diseases. However, some compounds, β-lactamase inhibitors, can block these enzymes allowing for possible treatments using a combination…

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The research aims to explore the evolutionary adaptability of enzymes and the impact of temperature on protein evolution pathways, using M. tuberculosis β-lactamase BlaC as the object of study. Enzymes inherently embody a delicate balance between activity and stability, and the acquisition of new enzymatic…

Due to the modern techniques of combinatorial chemistry and high-throughput screening, data on the biological activity of many millions of compounds is known. However, it is still very difficult to transfer this data into knowledge: if we know that compounds A and B bind to a certain protein with high…

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

Enzymes are innately sensitive to changes in the amino acid sequence, which largely constrains their evolutionary potential, i.e., evolvability. This evolutionary burden can be alleviated in the presence of stabilizing mutations, which increase the buffering capacity of enzymes to tolerate mutations…

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

In this thesis unconventional tools based on fluidic interfaces were developed to study the surface and interfacial chemistry of graphene, to characterize the intrinsic properties of graphene, to disentangle the effects of substrate and of the environmental factors, and to improve handling protocols…

This thesis focuses on developing wafer-scale two-dimensional (2D) materials by combining synthesis, transfer, characterization, and device integration of graphene, hexagonal boron nitride (h-BN), and BN-doped amorphous carbon.

Neurodegenerative diseases pose a large medical and societal challenge. The etiology of these diseases is still poorly understood, which makes drug discovery for these diseases difficult.

Lipid nanoparticles (LNPs) have enabled the success of mRNA vaccines but remain limited in broader therapeutic use by challenges in delivery efficiency, targeting, and mechanistic understanding.

This thesis describes the evaluation of novel natural products with antibacterial activity enabled by total chemical synthesis.

Division contact information & address

The drug BIA 10-2474 inhibits fatty acid amide hydrolase (FAAH), a lipase that degrades a specific endocannabinoid. On the basis of this activity, BIA 10-2474 was being developed as a potential treatment for anxiety and pain. In a phase 1 trial of the drug, one subject died, and four others suffered…

BACKGROUND: Explant human skin equivalents (Ex-HSEs) can be generated by placing a 4mm skin biopsy onto a dermal equivalent. The keratinocytes migrate from the biopsy onto the dermal equivalent, differentiate and form the epidermis of 1(st) generation Ex-HSEs. This is especially suitable for the expansion…

Several single-stranded RNA viruses make use of Xrn1-resistant RNAs in their 3’ untranslated regions of their genome RNAs in order to increase their pathogenicity.

The relative simplicity of the bacterial cell, short generation times and well defined and inexpensive culturing conditions have significantly contributed to our understanding of many complex biological systems. Yet the workings of the bacterial genome, seemingly impossibly compressed within a tiny…

Glycosidases (GHs) are enzymes responsible for the degradation of carbohydrates and play many roles in human health and pathophysiology. Often, abnormal levels of glycosidase activity are markedly linked to human pathologies.

A month ago it was Marc Baggelaar, and now Hans Kistemaker too has obtained his PhD cum laude at the Leiden Institute for Chemistry (LIC). ‘He has made ground-breaking contributions to the world of protein modification,’ says PhD supervisor Gijs van der Marel. Kistemaker obtained his PhD on 11 May…

Implementing all kinds of change and introducing new structures, far-reaching rules and administrative systems may sometimes seem to distract an organisation from its purpose. Furthermore, there is growing recognition of the need of staff of public organisations to find more meaning in their work: the…

That a switching protein plays a role in protecting a plant from too much sunlight was already known, but how exactly was not yet understood. The research group of Anjali Pandit has now discovered that this protein changes shape when there is too much sunlight. The results have been published in Nature…

Globally, the number of deaths from infections is on the rise as more bacteria become resistant to antibiotics. New classes are desperately needed. A promising resistance inhibitor is now being developed by the research group of Nathaniel Martin, Professor of Biological Chemistry. Inaugural speech on…

For her bachelor’s thesis, Molecular Science and Technology student Madouc Bergers synthesized her own molecule that can inhibit the breakdown of sugars. Although most students do not even manage to make one building block, Madouc made three. Partly because of this, she has been nominated for the Science…

The LED3 hub, consisting of researchers from the Leiden Institute of Chemistry (LIC), the Institute of Biology Leiden (IBL), the Leiden Academic Centre for Drug Research (LACDR) and the Leiden Institute of Advanced Computer Science (LIACS), is very excited to organize the “LED3 Lectures”. This lecture…

Three speakers, three fascinating science stories and a well-filled lecture hall. The Niko Tinbergen Lecture had a successful restart on 10 December 2019.