A5081381662- Peptidase Inhibition and Analysis
- Neuropeptides and Animal Physiology
- Diabetes Treatment and Management
- Signaling Pathways in Disease
- Protease and Inhibitor Mechanisms
- Enzyme Structure and Function
- Chemical Synthesis and Analysis
- Biochemical and Molecular Research
- Blood Coagulation and Thrombosis Mechanisms
- Erythrocyte Function and Pathophysiology
- Click Chemistry and Applications
- Trypanosoma species research and implications
- Chemokine receptors and signaling
- Oral and gingival health research
- Pneumocystis jirovecii pneumonia detection and treatment
- Pancreatic function and diabetes
- Parkinson's Disease Mechanisms and Treatments
- Hemoglobin structure and function
- Electrochemical sensors and biosensors
- Cardiac Structural Anomalies and Repair
- Biochemical and Structural Characterization
- Electrochemical Analysis and Applications
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Hormonal Regulation and Hypertension
- Adenosine and Purinergic Signaling
University of Antwerp
2015-2025
Weatherford College
2011-2013
HistoGeneX (Belgium)
2012
Statistics Belgium
2012
Erasmus MC
2007
Wilex (Germany)
2007
National Health Research Institutes
2007
University of Oulu
2002-2006
Euroscreen (Belgium)
2001
KU Leuven
1980-2001
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)...
Chemokines coordinate many aspects of leukocyte migration. As chemoattractants they play an important role in the innate and acquired immune response. There is good experimental evidence that N-terminal truncation by secreted or cell surface proteases a way modulating chemokine action. The localization CD26/dipeptidyl peptidase IV on surfaces biological fluids, its primary specificity, type naturally occurring truncated chemokines are consistent with such function. We determined steady-state...
Chemokines are key players in inflammation and infection. Natural forms of the C-X-C chemokine granulocyte chemotactic protein-2 (GCP-2) C-C regulated on activation normal T cell expressed secreted (RANTES), which miss two NH2-terminal residues, including a Pro penultimate position, have been isolated from leukocytes or tumor cells. In chemotaxis intracellular calcium mobilization assays, truncation caused reduction specific activity RANTES but not GCP-2. The serine protease...
Dipeptidyl peptidase IV (DPPIV, EC 3.4.14.5) is a serine type protease with an important modulatory activity on number of chemokines, neuropeptides and peptide hormones. It also known as CD26 or adenosine deaminase (ADA; 3.5.4.4) binding protein. DPPIV has been demonstrated the plasmamembranes T cells activated natural killer B well endothelial differentiated epithelial cells. A soluble form CD26/DPPIV described in serum. Over past few years, several related enzymes similar dipeptidyl have...
Site-specific substitutions of arginine for lysine in the thermostable D-xylose isomerase (XI) from Actinoplanes missouriensis are shown to impart significant heat stability enhancement presence sugar substrates most probably by interfering with nonenzymatic glycation. The same also found increase absence any derivatives, where a mechanism based on prevention glycation can no longer be invoked. This rather conservative substitution is moreover improve thermostability two other structurally...
Analysis of plasma B-type natriuretic peptide (BNP) has suggested the in vivo formation a truncated form, BNP (3-32), also called des-SerPro-BNP. The objectives this study were to investigate (a) whether and other peptides are by dipeptidyl-peptidase IV (DPP IV/CD26; EC 3.4.14.5) (b) truncation affects susceptibility cleavage neutral endopeptidase (NEP; 3.4.24.11).Human (1-32), A-type 1-28 (ANP 1-28), related incubated with purified DPP human plasma. In addition, ANP (1-28) subjected...
Prostaglandin H (PGH) synthase reacts with organic hydroperoxides and fatty acid on a millisecond time scale to generate an intermediate that is spectrally similar compound I of horseradish peroxidase. Compound PGH converted II within 170 ms. decays resting enzyme in few seconds. Thus, the peroxidase reaction appears involve cycle native enzyme, I, II, typical heme-containing peroxidases. The Soret absorption maximum occur at 412 nm but small amount may be present. maxima 420, 433, 419 for...
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 serine protease CD26/dipeptidyl-peptidase IV (CD26/DPP IV) and chemokines are known key players in immunological processes. Surprisingly, CD26/DPP not only removed the expected Gly1-Pro2 dipeptide from NH2 terminus of macrophage-derived chemokine (MDC) but subsequently also Tyr3-Gly4 dipeptide, generating MDC(5–69). This second cleavage after a Gly residue demonstrated that substrate specificity this is less restricted than anticipated. unusual processing MDC by was confirmed on...
The kinetics of colchicine binding to tubulin has been studied, using a fluorescence stopped flow.
The kinetics of the reaction H2O2 with compound II horseradish peroxidase were studied as a function pH at 25 degrees C and constant ionic strength 0.11 M. involves transient formation ferric superoxide anion first step followed by intermediate species to form III. Both reactions are also observed peracetic acid substrate, though amplitude was too small for rate be measured. Observation not possible below 8.5 under conditions this investigation. It tends occur faster lower so an increasing...
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...
Abstract α-Synuclein is an intrinsically disordered protein that can self-aggregate and plays a major role in Parkinson’s disease (PD). Elevated levels of certain metal ions are found aggregates neurons people suffering from PD, environmental exposure has also been linked with neurodegeneration. Importantly, cellular interactions ions, particularly Ca 2+ , have recently reported as key for α-synuclein’s physiological function at the pre-synapse. Here we study effects ion interaction...
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...
The dimeric enzyme triosephosphate isomerase (TIM) has a very tight and rigid dimer interface. At this interface critical hydrogen bond is formed between the main chain oxygen atom of catalytic residue Lys13 completely buried side Gln65 (of same subunit). sequence Leishmania mexicana TIM, closely related to Trypanosoma brucei TIM (68% identity), shows that highly conserved glutamine been replaced by glutamate. Therefore, 1.8 A crystal structure leishmania (at pH 5.9) was determined....
Dipeptidyl‐peptidase IV (DPPIV/CD26) metabolizes neuropeptides regulating insulin secretion. We studied the in vitro steady‐state kinetics of DPPIV/CD26‐mediated truncation vasoactive intestinal peptide (VIP), pituitary adenylyl cyclase‐activating (PACAP27 and PACAP38), gastrin‐releasing (GRP) neuropeptide Y (NPY). DPPIV/CD26 sequentially cleaves off two dipeptides VIP, PACAP27, PACAP38 GRP. GRP situates between best substrates reported, comparable to NPY. Surprisingly, C‐terminal extension...
In Trypanosoma brucei the enzyme glucose‐6‐phosphate isomerase, like most other enzymes of glycolytic pathway, resides in a microbody‐like organelle, glycosome. Here we report detailed study this enzyme, involving determination its kinetic properties and cloning sequence analysis gene. The gene codes for polypeptide 606 amino acids, with calculated M r 67280. protein predicted from has 54–58% positional identity yeast mammalian counterparts. Compared to those isomerases trypanosomal contains...
The kinetic properties of Trypanosoma brucei triose-phosphate isomerase are compared with those the commercially available rabbit muscle and yeast enzymes published data on chicken enzyme. With glyceraldehyde 3-phosphate as substrate Km= 0.25 ± 0.05 mM kcat= 3.7 × 105 min−1. dihydroxyacetone phosphate 1.2 0.1 6.5 104 pH dependence Km Vmax at M ionic strength is in agreement results for enzymes. At below effect a charged group specific trypanosomal enzyme absent from becomes detectable. This...