A5037582954- Peptidase Inhibition and Analysis
- Neuropeptides and Animal Physiology
- Diabetes Treatment and Management
- Protease and Inhibitor Mechanisms
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Signaling Pathways in Disease
- HIV/AIDS drug development and treatment
- Cardiac Structural Anomalies and Repair
- Radiopharmaceutical Chemistry and Applications
- Biochemical and Molecular Research
- Trypanosoma species research and implications
- Adenosine and Purinergic Signaling
- Medical Imaging Techniques and Applications
- Cell death mechanisms and regulation
- Mediterranean and Iberian flora and fauna
- African Botany and Ecology Studies
- Plant Taxonomy and Phylogenetics
- Indoor Air Quality and Microbial Exposure
- HIV Research and Treatment
- Pneumocystis jirovecii pneumonia detection and treatment
- Atmospheric chemistry and aerosols
- Crystallization and Solubility Studies
- Botany and Plant Ecology Studies
- Synthesis and Characterization of Heterocyclic Compounds
University of Antwerp
2016-2025
Ghent University
2007-2014
Queen Astrid Military Hospital
2010
Onze Lieve Vrouwziekenhuis Hospital
2010
California Institute of Technology
2009
Leibniz Institute for Tropospheric Research
2009
University of Stuttgart
2008
Erasmus MC
2007
Wilex (Germany)
2007
Research Triangle Park Foundation
2007
Highly oxygenated compounds assigned to be oxidation products of α ‐pinene have recently been observed in substantial concentrations ambient aerosols. Here, we confirm the unknown tracer compound with molecular weight (MW) 204 as C 8 ‐tricarboxylic acid 3‐methyl‐1,2,3‐butanetricarboxylic acid. Its gas and liquid chromatographic behaviors its mass spectral characteristics electron ionization negative ion electrospray perfectly agree those a synthesized reference compound. The formation this...
Detailed organic analysis of fine (PM2.5) rural aerosol collected during summer at K-puszta, Hungary from a mixed deciduous/coniferous forest site shows the presence polar oxygenated compounds that are also formed in laboratory irradiated alpha-pinene/NOx/air mixtures. In present work, two major photooxidation products alpha-pinene were characterized as hydroxydicarboxylic acids, 3-hydroxyglutaric acid, and 2-hydroxy-4-isopropyladipic based on chemical, chromatographic, mass spectral data....
Fibroblast activation protein (FAP) is a serine protease related to dipeptidyl peptidase IV (DPPIV). It has been convincingly linked multiple disease states involving remodeling of the extracellular matrix. FAP inhibition investigated as therapeutic option for several these diseases, with most attention so far devoted oncology applications. We previously discovered N-4-quinolinoyl-Gly-(2S)-cyanoPro scaffold possible entry highly potent and selective inhibitors. In present study, we explore...
Fibroblast activation protein (FAP) is a serine protease that generally accepted to play an important role in tumor growth and other diseases involving tissue remodeling. Currently there are no FAP inhibitors with reported selectivity toward both the closely related dipeptidyl peptidases (DPPs) prolyl oligopeptidase (PREP). We present discovery of new class N-(4-quinolinoyl)-Gly-(2-cyanopyrrolidine) scaffold. have explored effects substituting quinoline ring varying position its sp(2)...
Novel secondary organic aerosol (SOA) products from the monoterpene α-pinene with unique dimer-forming properties have been identified as lactone-containing terpenoic acids, i.e., terpenylic and 2-hydroxyterpenylic acid, diaterpenylic acid acetate. The structural characterizations were based on synthesis of reference compounds detailed interpretation mass spectral data. Terpenylic acetate are early oxidation generated upon both photooxidation ozonolysis, while is an abundant SOA tracer in...
Ferroptosis is an iron-catalyzed, nonapoptotic form of regulated necrosis that results in oxidative lipid damage cell membranes can be inhibited by the radical-trapping antioxidant Ferrostatin-1 (Fer-1). Novel inhibitors derived from Fer-1 scaffold ferroptosis potently but suffered solubility issues. In this paper, we report synthesis a more stable and readily soluble series analogues inhibit ferroptosis. The most promising compounds (37, 38, 39) showed improved protection compared to...
Ferroptosis is a nonapoptotic, iron-catalyzed form of regulated necrosis that critically dependent on glutathione peroxidase 4 (GPX4). It has been shown to contribute liver and kidney ischemia reperfusion injury in mice. A chemical inhibitor discovered by high-throughput screening displayed inhibition ferroptosis with nanomolar activity was dubbed ferrostatin-1 (fer-1). Ferrostatins inhibit oxidative lipid damage, but suffer from inherent stability problems due the presence an ester moiety....
Fibroblast activation protein (FAP) is a proline selective serine protease that overexpressed in tumor stroma and lesions of many other diseases are characterized by tissue remodeling. In 2014, most potent FAP-inhibitor (referred to as UAMC1110) with low nanomolar FAP-affinity high selectivity toward related enzymes such prolyl oligopeptidase (PREP) the dipeptidyl-peptidases (DPPs): DPP4, DPP8/9 DPP2 were developed. This inhibitor has been adopted recently groups create radiopharmaceuticals...
Radiopharmaceuticals based on the highly potent FAP inhibitor (FAPi) UAMC-1110 have shown great potential in molecular imaging, but short tumor retention time of monomers do not match physical half-lives important therapeutic radionuclides 177Lu and 225Ac. This was improved with dimer DOTAGA.(SA.FAPi)2, pharmacological radiolabeling properties still need optimization. Therefore, novel FAPi homodimers DO3A.Glu.(FAPi)2 DOTAGA.Glu.(FAPi)2. were synthesized quantitatively radiolabeled 68Ga, 90Y,...
Crohn's disease (CD) is marked by recurring intestinal inflammation and tissue injury, often resulting in fibrostenosis bowel obstruction, necessitating surgical intervention with high recurrence rates. To elucidate the mechanisms underlying CD, we analyzed transcriptome of cells isolated from transmural ileum patients including a trio lesions each patient: non-affected, inflamed, stenotic samples, compared them samples without CD. Our computational analysis revealed that profibrotic signals...
The feasibility of the fluoro-olefin function as a peptidomimetic group in inhibitors for dipeptidyl peptidase IV and II (DPP DPP II) is investigated by evaluation N-substituted Gly-Psi[CF=C]pyrrolidines, Gly-Psi[CF=C]piperidines, Gly-Psi[CF=C](2-cyano)pyrrolidines. Of this later class, (Z)- (E)-fluoro-olefin analogues were prepared chemical stability comparison with parent amide was checked. Most these compounds exhibited strong binding preference toward IC(50) values low micromolar range,...
The aggregation of α-synuclein is connected to the pathology Parkinson's disease and prolyl oligopeptidase (PREP) accelerates in vitro. aim this study was investigate effects a PREP inhibitor, KYP-2047, on cell lines overexpressing wild-type or A30P/A53T mutant human α-syn brains two A30P transgenic mouse strains.Cells were exposed oxidative stress then incubated with inhibitor during after stress. Wild-type mice treated for 5 days KYP-2047 (2 × 3 mg·kg(-1) day). Besides immunohistochemistry...
Necroptosis contributes to the pathophysiology of several inflammatory, infectious and degenerative disorders. TNF-induced necroptosis involves activation receptor-interacting protein kinases 1 3 (RIPK1/3) in a necrosome complex, eventually leading phosphorylation relocation mixed lineage kinase domain like (MLKL). Using high-content screening small compounds FDA-approved drug libraries, we identified anti-cancer Sorafenib tosylate as potent inhibitor TNF-dependent necroptosis....
RATIONALE A considerable fraction of atmospheric particulate fine matter consists organosulfates, with some the most polar ones originating from oxidation isoprene. Their structural characterization provides insights into nature gas‐phase precursors as well formation pathways. METHODS The structures unknown organosulfates present in ambient were characterized using liquid chromatography/(−)electrospray ionization mass spectrometry (LC/(−)ESI‐MS), including ion trap MS n and accurate...
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a fibrotic stroma with poor lymphocyte infiltrate, in part driven cancer-associated fibroblasts (CAFs). CAFs, which express fibroblast activation protein (FAP), contribute to immune escape via exclusion of anti-tumor CD8+ T cells from cancer cells, upregulation checkpoint ligand expression, immunosuppressive cytokine production, and polarization tumor infiltrating inflammatory cells. FAP post-proline peptidase selectively expressed...
Activating germline mutations in the human inflammasome sensor NLRP1 causes palmoplantar dyskeratosis and susceptibility to Mendelian autoinflammatory diseases. Recent studies have shown that cytosolic serine dipeptidyl peptidases DPP8 DPP9 suppress activation upstream of CARD8 keratinocytes peripheral blood mononuclear cells. Moreover, pharmacological inhibition DPP8/DPP9 protease activity was induce pyroptosis murine C57BL/6 macrophages without eliciting other hallmark responses. Here, we...
A series of chloro- and aminoalkylamino-substituted neocryptolepine (5-methyl-5H-indolo[2,3-b]quinoline) derivatives were synthesized evaluated as antiplasmodial agents. The evaluation also included cytotoxicity (MRC5 cells), inhibition β-hematin formation, DNA interactions (DNA−methyl green assay). Introduction aminoalkylamino chains increased the activity core substantially. most efficient compounds showed activities in nanomolar range....