A5048858774- Peptidase Inhibition and Analysis
- Protease and Inhibitor Mechanisms
- Ubiquitin and proteasome pathways
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Blood Coagulation and Thrombosis Mechanisms
- Biochemical and Structural Characterization
- Mosquito-borne diseases and control
- Glycosylation and Glycoproteins Research
- Antimicrobial Resistance in Staphylococcus
- Inflammatory Bowel Disease
- Cell Adhesion Molecules Research
- Protein Hydrolysis and Bioactive Peptides
- Bladder and Urothelial Cancer Treatments
- Cancer, Lipids, and Metabolism
- Parathyroid Disorders and Treatments
- Cerebrovascular and genetic disorders
- Advanced Proteomics Techniques and Applications
- Renal Diseases and Glomerulopathies
- Malaria Research and Control
- Iron Metabolism and Disorders
- Genetic and Kidney Cyst Diseases
- Inflammatory Biomarkers in Disease Prognosis
- Cholinesterase and Neurodegenerative Diseases
- Phosphodiesterase function and regulation
- Renewable energy and sustainable power systems
University of Gdańsk
2016-2025
Staphylococcus aureus is a dangerous human pathogen. A number of the proteins secreted by this bacterium are implicated in its virulence, but many components secretome poorly characterized. Strains S. can produce up to six homologous extracellular serine proteases grouped single spl operon. Although SplA, SplB, and SplC have been thoroughly characterized, properties other three enzymes not yet investigated. Here, we describe biochemical structural characteristics SplD protease. The active...
Microalbuminuria is the earliest clinical abnormality in diabetic kidney disease. High glucose (HG) concentrations are associated with induction of oxidative stress podocytes, leading to disruption glomerular filtration barrier. Our recent study revealed a significant decrease membrane-bound fraction Klotho podocytes that were cultured under HG conditions. Given disintegrin and metalloproteinase 17 (ADAM17) responsible for shedding from cell membrane, present investigated impact on interplay...
Neutrophil serine proteases, including elastase, proteinase 3, and cathepsin G, are closely related enzymes stored in similar amounts azurophil granules released at the same time from triggered neutrophils inflammatory sites. We have synthesized new fluorescence resonance energy transfer (FRET) substrates with different donor-acceptor pairs that allow all three proteases to be quantified reaction mixture. This was made possible because emission spectra of donors do not overlap values...
Kallikrein 13 (KLK13) was first identified as an enzyme that is downregulated in a subset of breast tumors. This serine protease has since been implicated number pathological processes including ovarian, lung and gastric cancers. Here we report the design, synthesis deconvolution libraries internally quenched fluorogenic peptide substrates to determine specificity substrate binding subsites KLK13 prime non-prime regions (according Schechter Berger convention). The with consensus sequential...
A growing body of evidence suggests a role proteolytic enzymes in the development diabetic nephropathy. Cathepsin C (CatC) is well-known regulator inflammatory responses, but its involvement podocyte and renal injury remains obscure. We used Zucker rats, genetic model metabolic syndrome insulin resistance, to determine presence, quantity, activity CatC urine. In addition animal study, we two cellular models, immortalized human podocytes primary rat podocytes, mRNA protein expression levels...
The neutrophilic serine protease proteinase 3 (PR3) is involved in inflammation and immune response thus appears as a therapeutic target for variety of infectious inflammatory diseases. Here we combined kinetic molecular docking studies to increase the potency peptidyl-diphenyl phosphonate PR3 inhibitors. Occupancy S1 subsite by nVal residue S4–S5 subsites biotinylated Val obtained biotin-VYDnVP(O-C6H4-4-Cl)2 enhanced second-order inhibition constant kobs/[I] toward more than 10 times...
The 20S catalytic core of the human 26S proteasome can be secreted from cells, and high levels extracellular have been linked to many types cancers autoimmune diseases. Several diagnostic approaches developed that detect activity in plasma, but these suffer problems with efficiency sensitivity. In this report, we describe optimization synthesis an internally quenched fluorescent substrate proteasome, investigate its use as a potential test bladder cancer. This peptide, 2-aminobenzoic acid...
Abstract Herein we present the synthesis of a novel type peptidomimetics composed repeating diaminopropionic acid residues modified with structurally diverse heterobifunctional polyethylene glycol chains (abbreviated as DAPEG). Based on developed compounds, library fluorogenic substrates was synthesized. Further deconvolution towards human neutrophil serine protease 4 (NSP4) yielded highly sensitive and selective internally quenched peptidomimetic substrates. In silico analysis obtained...
Accumulating evidence suggests that six proteases encoded in the spl operon of a dangerous human pathogen, Staphylococcus aureus, may play role virulence. Interestingly, SplA, B, D, and E have complementary substrate specificities while SplF remains to be characterized this regard. Here, we describe prerequisites heterologous expression system for active protease characterize enzyme terms specificity its structural determinants. Substrate is comprehensively profiled using combinatorial...
Although the mosquito-borne Zika virus was discovered in late 1940s of 20th century, for years it neglected, as disease humans rare and relatively mild. Viral NS2B-NS3 protease is essential replication, except maturation viral proteins, also modulates infection microenvironment to facilitate invasion. Here, we report combinatorial chemistry approach synthesis internally quenched substrates that were optimized prime positions peptide chain. Final substrate...
Kallikrein-related peptidases (KLKs) and matrix metalloproteinases (MMPs) are secretory proteinases known to proteolytically process components of the extracellular matrix, modulating pericellular environment in physiology pathologies. The interconnection between these families remains elusive. To assess cross-activation families, we developed a peptide, fusion protein-based exposition system (Cleavage exposed amino acid sequences, CleavEx) aiming at investigating potential KLK14 recognize...
Increased protease activity has been linked to the pathogenesis of IBD. While most studies have focusing on host proteases in gut inflammation, it remains unclear how address potential contribution their bacterial counterparts. In present study, we report a functional characterization newly identified serine protease, SP-1, from human microbiota. The repertoire
This work describes the chemical synthesis, combinatorial selection, and enzymatic evaluation of peptidomimetic fluorescent substrates specific for trypsin-like (β2) subunit 20S human proteasome. After deconvolution a library comprising nearly 6000 compounds composed peg substituted diaminopropionic acid DAPEG building blocks, sequence ABZ–Dap(O2(Cbz))–Dap(GO1)–Dap(O2(Cbz))–Arg–ANB–NH2, where ABZ is 2-aminobenzoic acid, ANB- 5 amino 2- nitro benzoic was selected. Its cleavage followed...
Abstract Bladder cancer (BC) is the sixth common in world, characterized by high recurrent rate and poor prognosis. In most cases asymptomatic it can take years until symptoms develop. What more, diagnosed patients need regular re‐examinations which are invasive expensive. Here, we used chromogenic substrates for qualitative determination of specific activity urine enzymes healthy bladder patients. The peptide ABZ‐Met‐Lys‐Val‐Trp‐ANB‐NH 2 appears at low absorbance 410 nm. During hydrolysis,...
Cancer development and progression is often associated with inflammation. Late diagnosis of inflammation that directly leads to the neoplasm-cancer a reduction in chance successful treatment or therapeutic difficulties. A panel chromogenic substrates was used for qualitative determination specific activity enzymes urine patients confirmed inflammatory reaction and/or epithelial neoplasms particular tumours at various stages development. Urine people excluded as control group. Proteolytic...
Antimicrobial peptides are part of the innate immune response, regulate inflammation and initiate acquired immunity. This study focused on theta-defensins that have been shown to anticancer properties.RTD-2 analogs were synthesized a peptide synthesizer. Cell viability was estimated using MTT test. Immunoprecipitation assay conducted determine molecular partner [Ser3,7,12,16]-RTD-2 analog.Here, we present biologically active analog selectively targets various types breast cancer cells....