A5022246263- Enzyme Structure and Function
- Biochemical and Molecular Research
- HIV/AIDS drug development and treatment
- Protein Structure and Dynamics
- Computational Drug Discovery Methods
- Lung Cancer Treatments and Mutations
- Malaria Research and Control
- Monoclonal and Polyclonal Antibodies Research
- Ubiquitin and proteasome pathways
- Chemical Synthesis and Analysis
- Plant biochemistry and biosynthesis
- Enzyme Production and Characterization
- Mass Spectrometry Techniques and Applications
- Advanced Proteomics Techniques and Applications
- Cancer Genomics and Diagnostics
- Pneumocystis jirovecii pneumonia detection and treatment
- Microbial Natural Products and Biosynthesis
- SARS-CoV-2 and COVID-19 Research
- Colorectal Cancer Treatments and Studies
- Protein purification and stability
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Lung Cancer Research Studies
- Biochemical and Structural Characterization
- Photosynthetic Processes and Mechanisms
University of Groningen
2016-2025
North Carolina Agricultural and Technical State University
2022
University Medical Center Groningen
2017-2022
Institute of Biostructure and Bioimaging
2022
Dialyse Centrum Groningen
2021
William & Mary
2019
Williams (United States)
2019
European Molecular Biology Laboratory
2006-2015
Deutsches Elektronen-Synchrotron DESY
2015
European Molecular Biology Laboratory
2007-2013
The rapid growth of COVID-19 cases is causing an increasing death toll and also paralyzing the world economy. De novo drug discovery takes years to move from idea and/or pre-clinic market, it not a short-term solution for current SARS-CoV-2 pandemic. Drug repurposing perhaps only solution, while vaccination middle-term solution. Here, we describe path HCV NS3-4A protease inhibitors boceprevir telaprevir as main (3CLpro) inhibitors. Based on our hypothesis that α-ketoamide drugs can...
DNA-encoded combinatorial synthesis provides efficient and dense coverage of chemical space around privileged molecular structures. The indole side chain tryptophan plays a prominent role in key, or "hot spot", regions protein-protein interactions. A peptoid library was designed based on the Ugi four-component reaction by employing tryptophan-mimetic chains to probe surface target proteins. Several peptoids were synthesized chemically stable hexathymidine adapter oligonucleotide "hexT",...
Protein tyrosine phosphatases regulate diverse cellular processes and represent important targets for therapeutic intervention in a number of diseases. The crystal structures protein phosphatase 1B (PTP1B) complex with small molecule inhibitors based upon two classes phosphotyrosine mimetics, the (difluoronaphthylmethyl)phosphonic acids fluoromalonyl tyrosines, have been determined to resolutions greater than 2.3 Å. residue was incorporated within cyclic hexapeptide modeled on an...
Bacteria are permanently in contact with reactive oxygen species (ROS), both over the course of their life cycle as well that present environment. These cause damage to proteins, lipids, and nucleotides, negatively impacting organism. To detect these ROS molecules stimulate expression proteins involved antioxidative stress response, bacteria use a number different protein-based regulatory sensory systems. ROS-based detection mechanisms induce posttranslational modifications, resulting...
Miniaturization and acceleration of synthetic chemistry are critically important for rapid property optimization in pharmaceutical, agrochemical, materials research development. However, most laboratories organic synthesis is still performed on a slow, sequential, material-consuming scale not validated multiple substrate combinations. Herein, we introduce fast touchless acoustic droplet ejection (ADE) technology into small-molecule to transfer building blocks by nL droplets scout newly...
Abstract Stapled peptides are chemical entities in‐between biologics and small molecules, which have proven to be the solution high affinity protein–protein interaction antagonism, while keeping control over pharmacological performance such as stability membrane penetration. We demonstrate that multicomponent reaction‐based stapling is an effective strategy for development of α‐helical with highly potent dual antagonistic action MDM2 MDMX binding p53. Such a inhibitory activity p53‐MDM2/X...
Molecular tumor boards (MTBs) provide physicians with a treatment recommendation for complex tumor-specific genomic alterations. National and international consensus to reach is lacking. In this article, we analyze the effectiveness of an MTB decision-making methodology patients non-small-cell lung cancer (NSCLC) rare or mutational profiles as implemented in University Medical Center Groningen (UMCG).The UMCG-MTB comprises (pulmonary) oncologists, pathologists, clinical scientists molecular...
The SARS-CoV-2 viral spike protein S receptor-binding domain (S-RBD) binds ACE2 on host cells to initiate molecular events, resulting in intracellular release of the genome. Therefore, antagonists this interaction could allow a modality for therapeutic intervention. Peptides can inhibit S-RBD:ACE2 by interacting with protein-protein interface. In study, contact atlas data and dynamics simulations were used locate hotspots secondary structure elements α1, α2, α3, β3, β4 ACE2. We designed...
Abstract The chloroplast signal recognition particle (cpSRP) and its receptor (cpFtsY) target proteins both cotranslationally posttranslationally to the thylakoids. This dual function enables cpSRP utilize posttranslational activities for targeting a family of nucleus-encoded light-harvesting chlorophyll binding (LHCPs), most abundant membrane in plants. Previous vitro experiments indicated an absolute requirement all pathway soluble components. In agreement, cpFtsY mutant Arabidopsis...
Abstract SUL-compounds are protectants from cold-induced ischemia and mitochondrial dysfunction. We discovered that adding SUL-121 to renal grafts during warm machine reperfusion elicits a rapid improvement in perfusion parameters. Therefore, we investigate the molecular mechanisms of action porcine intrarenal arteries (PIRA). Porcine kidneys were stored on ice overnight parameters recorded treatment with SUL-compounds. Agonist-induced vasoconstriction was measured isolated PIRA after...
Human milk oligosaccharides (hMOs) can attenuate inflammation by modulating intestinal epithelial cells, but the mechanisms of action are not well-understood. Here, effects hMOs on tumor necrosis factor-α (TNF-α) induced inflammatory events in gut cells studied.The modulatory 2'-fucosyllactose, 3-fucosyllactose (3-FL), 6'-sialyllactose, lacto-N-tetraose, lacto-N-neotetraose (LNnT), lactodifucotetraose (LDFT), and lacto-N-triaose (LNT2) immature (FHs 74 Int) adult (T84) with or without TNF-α...