A5009982249- Peptidase Inhibition and Analysis
- Neuropeptides and Animal Physiology
- Diabetes Treatment and Management
- Protease and Inhibitor Mechanisms
- Signaling Pathways in Disease
- Chemokine receptors and signaling
- Cardiac Structural Anomalies and Repair
- Glycosylation and Glycoproteins Research
- Chemical Synthesis and Analysis
- Adenosine and Purinergic Signaling
- Transplantation: Methods and Outcomes
- Ubiquitin and proteasome pathways
- Pneumocystis jirovecii pneumonia detection and treatment
- Oral and gingival health research
- Heart Failure Treatment and Management
- Hormonal Regulation and Hypertension
- Radiopharmaceutical Chemistry and Applications
- Stress Responses and Cortisol
- Tryptophan and brain disorders
- Antimicrobial Peptides and Activities
- Cancer Immunotherapy and Biomarkers
- Gastrointestinal motility and disorders
- Biochemical and Structural Characterization
- Cell Adhesion Molecules Research
- Infant Nutrition and Health
University of Antwerp
2016-2025
Laboratoire de Biochimie
2015
University of Padua
2013
Cipla (Belgium)
2012
KU Leuven
1994-2007
National Health Research Institutes
2007
Rega Institute for Medical Research
1998-2006
Instituto de Química Médica
2006
Institut Curie
2001
Inserm
2001
Many biologically important peptide sequences contain proline. It confers unique conformational constraints on the chain in that side-chain is cyclized back onto backbone amide position. Inside an alpha-helix possibility of making hydrogen bonds to preceding turn lost and a kink will be introduced. The restrictions imposed by proline motifs appear imply structural or biological functions as can deduced from their often remarkably high degree conservation found many proteins peptides,...
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...
The chemokine stromal‐cell‐derived factor‐1α (SDF‐1α) chemoattracts lymphocytes and CD34 + haematopoietic progenitors is the ligand for CXCR4 (CXC receptor 4), main co‐receptor T‐tropic HIV‐1 strains. SDF‐1α was NH 2 ‐terminally cleaved to SDF‐1α(3‐68) by dipeptidyl‐peptidase IV (CD26/DPP IV), which present in blood soluble membrane‐bound form. lost both lymphocyte chemotactic CXCR4‐signaling properties. However, still desensitized SDF‐1α(1‐68)‐induced Ca 2+ response. In contrast CD26/DPP...
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...
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 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...
Chemokines attract and activate distinct sets of leukocytes. The CC chemokine eotaxin has been characterized as an important mediator in allergic reactions because it selectively attracts eosinophils, Th2 lymphocytes, basophils. Human a penultimate proline, indicating that might be substrate for dipeptidyl-peptidase IV (CD26/DPP IV). In this study we demonstrate is efficiently cleaved by CD26/DPP the NH2-terminal truncation affects its biological activity. IV-truncated eotaxin(3-74) showed...
Human Monocyte Chemotactic Protein (MCP)-2 has originally been isolated from stimulated osteosarcoma cells as a chemokine coproduced with MCP-1 and MCP-3. Here, 5'-end extended MCP-2 cDNA was cloned human testis library. It encoded 76 residue protein, but differed the reported bone marrow-derived sequence in codon 46, which coded for Lys instead of Gln. This MCP-2Lys46 variant, caused by single nucleotide polymorphism (SNP), biologically compared MCP-2Gln46. The coding regions were subcloned...
Selective leukocyte trafficking towards sites of inflammation is mediated by chemokines. RANTES a CC chemokine that attracts lymphocytes, monocytes, dendritic cells, eosinophils, basophils and NK cells. A natural form human lacking two N-terminal residues was isolated from stimulated sarcoma fibroblasts, leukocytes. RANTES(3 – 68) showed more than tenfold reduction in chemotactic potency for monocytes eosinophils. To elucidate the mechanism involved, receptor recognition studies were...
The aim of the present study was to examine effects academic examination stress on leukocyte subset distribution in university students. Thirty-eight students had repeated blood collections for white cell differentiation and flow cytometric assay lymphocytic subsets a few weeks before after (i.e. two baseline conditions) as well day difficult condition). Flow cytometry used determine number peripheral mononuclear cells (PBMC). In students, who were reactors psychological (criterion based...