A5038766554- Cellular transport and secretion
- Alzheimer's disease research and treatments
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Enzyme function and inhibition
- Chemical Synthesis and Analysis
- DNA Repair Mechanisms
- Microtubule and mitosis dynamics
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Cannabis and Cannabinoid Research
- Peptidase Inhibition and Analysis
- Renal and related cancers
- Mitochondrial Function and Pathology
- Endoplasmic Reticulum Stress and Disease
- Computational Drug Discovery Methods
- Biochemical and Structural Characterization
- Pancreatic function and diabetes
- Epigenetics and DNA Methylation
- Biosimilars and Bioanalytical Methods
- Renal cell carcinoma treatment
- Biotin and Related Studies
- Ultrasound in Clinical Applications
- Protist diversity and phylogeny
- Protein Tyrosine Phosphatases
- PARP inhibition in cancer therapy
- Immune cells in cancer
Hycult Biotech (Netherlands)
2017
Radboud University Nijmegen
1995-2010
Radboud University Medical Center
2007-2010
University Medical Center
2004
Netherlands Institute for Neuroscience
1998
Erasmus University Rotterdam
1998
University Medical Center Utrecht
1998
Louisiana State University
1995
University Medical Center New Orleans
1995
The cerebral cortex of Alzheimer's and Down syndrome patients is characterized by the presence protein deposits in neurofibrillary tangles, neuritic plaques, neuropil threads. These structures were shown to contain forms β amyloid precursor ubiquitin-B that are aberrant (+1 proteins) carboxyl terminus. +1 proteins not found young control patients, whereas elderly may indicate early stages neurodegeneration. two species displayed cellular colocalization, suggesting a common origin, operating...
Monoacylglycerol lipase (MAGL) regulates endocannabinoid 2-arachidonoylglycerol (2-AG) and eicosanoid signalling. MAGL inhibition provides therapeutic opportunities but clinical potential is limited by central nervous system (CNS)-mediated side effects. Here, we report the discovery of LEI-515, a peripherally restricted, reversible inhibitor, using high throughput screening medicinal chemistry programme. LEI-515 increased 2-AG levels in peripheral organs, not mouse brain. attenuated liver...
Abstract Background and Purpose The C‐type lectin‐like receptor‐2 (CLEC‐2) is a platelet receptor for the endogenous ligand podoplanin. This interaction contributes to several (patho)physiological processes, such as lymphangiogenesis, preservation of blood lymphatic vessel integrity organ development, tumour metastasis. Activation CLEC‐2 leads phosphorylation its cytoplasmic hemITAM domain initiates signalling cascade involving kinase Syk. aim this study was identify characterise novel small...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnzymic characterization of immunopurified prohormone convertase 2: Potent inhibition by a 7B2 peptide fragmentIris Lindberg, Wilhelmina H. van den Hurk, Chau Bui, and Christopher J. BatieCite this: Biochemistry 1995, 34, 16, 5486–5493Publication Date (Print):April 25, 1995Publication History Published online1 May 2002Published inissue 25 April 1995https://pubs.acs.org/doi/10.1021/bi00016a020https://doi.org/10.1021/bi00016a020research-articleACS...
The highly conserved polypeptide 7B2 and the subtilisin-related prohormone convertases PC1/PC3 PC2 are broadly distributed in neurons endocrine cells localized to secretory granules. We recently showed that recombinant is vitro a potent inhibitor of activity, but not PC1/PC3, newly synthesized transiently associated with proPC2 vivo. In present study, mutagenesis was used identify region within sequence responsible for inhibition PC2. Mutant proteins were produced prokaryotic expression...
Previously, we identified the mitotic arrest deficient protein MAD2B (MAD2L2) as a bona fide interactor of renal cell carcinoma (RCC)-associated PRCC. In addition, found that fusion PRCC with transcription factor TFE3 in t(X;1)(p11;q21)-positive RCCs results an impairment this interaction and, concomitantly, abrogation cycle progression. Although is thought to inhibit anaphase promoting complex (APC) by binding CDC20 and/or CDH1(FZR1), its exact role control still remains be...
Background Although the mitotic arrest deficient protein MAD2B (MAD2L2) is thought to inhibit anaphase promoting complex (APC) by binding CDC20 and/or CDH1 (FZR1), its exact role in cell cycle control still remains be established. Methodology/Principal Findings Using a yeast two-hybrid interaction trap we identified human clathrin light chain A (CLTA) as novel protein. direct was established mammalian cells via GST pull-down and endogenous co-immunoprecipitation during G2/M phase of cycle....
Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins. Aberrant expression KLK6 has been found in different cancers and neurodegenerative diseases, currently studied as potential target these pathologies. We report novel series inhibitors discovered high-throughput screen within European Lead Factory program. Structure-guided design based on docking studies enabled rapid progression hit cluster with improved potency, selectivity...
Introduction Respiratory viruses causing lower respiratory tract infections (LRTIs) are a major cause of hospital admissions in children. Since the course these is unpredictable with potential fast deterioration into failure, infants easily admitted to for observation. The aim this study was examine whether systemic inflammatory markers can be used predict severity disease children viral infections. Methods Blood and nasopharyngeal washings from <3 years age LRTI attending were collected...
Antiplatelet drugs targeting G-protein-coupled receptors (GPCRs), used for the secondary prevention of arterial thrombosis, coincide with an increased bleeding risk. Targeting ITAM-linked receptors, such as collagen receptor glycoprotein VI (GPVI), is expected to provide a better antithrombotic-hemostatic profile. Here, we developed and characterized ultra-high-throughput (UHT) method based on intracellular [Ca2+]i increases differentiate GPVI GPCR effects platelets. In 96-, 384-, or...
The three human SNM1 metallo-β-lactamase fold nucleases (SNM1A-C) play key roles in DNA damage repair and maintaining telomere integrity. Genetic studies indicate that they are attractive targets for cancer treatment to potentiate chemo- radiation-therapy. A high-throughput screen SNM1A inhibitors identified diverse pharmacophores, some of which were shown by crystallography coordinate the di-metal ion centre at active site. Structure turnover assay-guided optimization enabled identification...
Distinct platelet activation patterns are elicited by the tyrosine kinase-linked collagen receptor glycoprotein VI (GPVI) and G-protein coupled protease-activated receptors (PAR1/4) for thrombin. This is reflected in different Ca2+ responses induced GPVI agonist collagen-related peptide (CRP) PAR1/4 Using a 96 well-plate assay with human Calcium-6-loaded platelets panel of 22 pharmacological inhibitors, we assessed cytosolic signaling domains these developed an automated curve algorithm. The...
The European Lead Factory (ELF) consortium provides academics and small medium enterprises access to ~0.5 million unique compounds, a state-of-the-art ultra-high-throughput screening (u-HTS) platform, industrial early drug discovery (DD) expertise with the aim of delivering innovative DD starting points. From 2013 2018, 154 proposals for eight target classes in seven therapeutic areas were submitted ELF consortium, 88 which accepted by selection committee. During this period, 76 primary...
Arginase-1, which converts the amino acid L-arginine into L-ornithine and urea, is a promising new drug target for cancer immunotherapy, as it has role in regulation of T-cell immunity tumor microenvironment. To enable discovery small-molecule Arginase-1 inhibitors by high-throughput screening, we developed novel homogeneous (mix-and-measure) fluorescence-based activity assay. The assay measures conversion decrease fluorescent signal due to quenching probe, Arginase Gold. This way,...
Abstract The amyloid‐β precursor protein (APP) is linked to Alzheimer's disease through its pathological proteolytic processing in the secretory pathway. Nevertheless, surprisingly little known about biosynthesis of endogenous APP. We therefore decided investigate intracellular fate newly synthesized APP a physiologically inducible neuroendocrine cell, Xenopus intermediate pituitary melanotrope cell. found that level both mRNA and was threefold induced activated cells black‐adapted animals....
Recently we found that the human papillary renal cell carcinoma-associated protein PRCC interacts with cycle control Mad2B, and translocates this to nucleus where it exerts its mitotic checkpoint function. Here have succesfully isolated <i>Xenopus laevis</i> Mad2B cDNAs. The full-length xMad2B cDNA encodes a 211 amino acid is highly homologous thus pointing an important function for in higher eukaryotes. xPRCC 544 protein. Remarkably, contains amino-terminal region distinct from...