A5063106007- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Organophosphorus compounds synthesis
- Cell Adhesion Molecules Research
- Animal health and immunology
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Herpesvirus Infections and Treatments
- Virology and Viral Diseases
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Ubiquitin and proteasome pathways
- Toxin Mechanisms and Immunotoxins
- HIV Research and Treatment
- T-cell and B-cell Immunology
- Carbohydrate Chemistry and Synthesis
- Mosquito-borne diseases and control
- S100 Proteins and Annexins
- Hepatitis C virus research
- Systemic Lupus Erythematosus Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Antimicrobial Resistance in Staphylococcus
- Biochemical and Structural Characterization
- Enzyme Production and Characterization
Wrocław University of Science and Technology
2015-2024
AGH University of Krakow
2014-2024
Weatherford College
2014
The University of Texas Health Science Center at Houston
2009-2010
Diaryl esters of α-aminophosphonates are a group low molecular weight inhibitors serine proteases. For over 30 years these molecules have captured the attention biochemists and medicinal chemists due to their similarity transition state peptide bond cleavage observed in enzymatic reactions (transition analogs) as well high potency action. High reactivity toward proteases complete lack activity against cysteine or threonine give great advantage other classes such chloromethyl ketones peptidyl...
The malaria parasite Plasmodium falciparum employs two metallo-aminopeptidases, PfA-M1 and PfA-M17, which are essential for survival. Compounds that inhibit the activity of either enzyme represent leads development new antimalarial drugs. Here we report synthesis structure-activity relationships a small library phosphonic acid arginine mimetics probe S1 pocket both enzymes map necessary interactions would be important dual inhibitor.
Herein, we present the synthesis and measurement of inhibitory activity novel peptidyl derivatives α-aminoalkylphosphonate diaryl esters as human neutrophil elastase inhibitors. Their selectivity against other serine proteases, including porcine pancreatic elastase, chymotrypsin, trypsin, was also demonstrated. We describe preparation single peptide diastereomers. The most active selective compound developed possessed a kinact/KI 2353000 M–1 s–1, which is potent irreversible inhibitor...
Background: A previous study showed that prebiotics and synbiotics administered in ovo into the egg air cell on 12th day of incubation enhance growth development chickens.However, influence this procedure efficiency innate immune system broiler chickens is unclear.Therefore, aim was to evaluate whether early (on embryo development) administration selected (inulin -Pre1 Bi 2 tos -Pre2) + Lactococcus lactis subsp.lactis IBB SL1 -Syn1 L. subsp.cremoris SC1 -Syn2) influences system.Results:...
The function of neutrophil protease 3 (PR3) is poorly understood despite its role in autoimmune vasculitides and possible involvement cell apoptosis. This makes it different from structural homologue elastase (HNE). Endogenous inhibitors human serine proteases preferentially inhibit HNE to a lesser extent, PR3. We constructed single-residue mutant PR3 (I217R) investigate the S4 subsite preferences used best peptide substrate sequences develop selective phosphonate with structure...
The effect of the in ovo application selected prebiotics and synbiotics on humoral immune response against T-dependent (SRBC) T-independent (dextran) antigens delayed-type hypersensitivity (DTH) to phytohemagglutinin was studied. On 12th day incubation, 800 eggs (Ross 308) were divided into five groups injected egg air chamber with prebiotic inulin (Pre1), Bi2tos (Pre2), a synbiotic composed Lactococcus lactis subsp. IBB SL1 (Syn1), L. cremoris SC1 (Syn2), physiological saline (control...
To identify an HIV epitope suitable for vaccine development.Diverse HIV-1 strains express few structurally constant regions on their surface vulnerable to neutralizing antibodies. The mostly conserved CD4-binding site (CD4BS) of gp120 is essential host cell binding and infection by the virus. Antibodies that recognize CD4BS are rare, one component CD4BS, 421-433 peptide region, expresses B-cell superantigenic character, a property predicted impair anti-CD4BS adaptive immune response.IgA...
Early detection of cancer development is crucial for successful therapy and monitoring patient outcome. Various immunodiagnostic methods are able to detect pathological changes in the human body ahead symptomatic manifestation disease. Most immunological examinations based on specific tumor markers fluids. Of various cancer-specific proteins used breast diagnostics, one most commonly applied antigen 15-3 (CA 15-3). An elevation its serum level (>25-40 U/ml) usually correlates with...
Protease-mediated degradation of proteins is critical in a plethora physiological processes. Neutrophils secrete serine proteases including cathepsin G (CatG), neutrophile elastase (NE), and proteinase 3 (PR3) together with lactoferrin (LF) as first cellular immune response against pathogens. Here, we demonstrate that LF increases the catalytic activity CatG at concentration, its highest enhancing capacity under acidic (pH 5.0) conditions, broadens substrate selectivity CatG. On functional...
Herpes simplex virus type 1 (HSV-1) is a widespread human pathogen known to cause infections of diverse severity, ranging from mild ulceration mucosal and dermal tissues life-threatening viral encephalitis. In most cases, standard treatment with acyclovir sufficient manage the disease progression. However, emergence ACV-resistant strains drives need for new therapeutics molecular targets. HSV-1 VP24 protease indispensable assembly mature virions and, as such, constitutes an interesting...
Autoantigenic peptides resulting from self-proteins such as proinsulin are important players in the development of type 1 diabetes mellitus (T1D). Self-proteins can be processed by cathepsins (Cats) within endocytic compartments and loaded to major histocompatibility complex (MHC) class II molecules for CD4(+) T cell inspection. However, processing presentation antigen-presenting cells (APC) humans is only partially understood. Here we demonstrate that B or myeloid dendritic (mDC1)-derived...
Measurement of serum prostate specific antigen (PSA) concentrations remains one the leading methods for diagnosing cancer. We developed and evaluated an immunoglobulin Y (IgY)-based ELISA to measure total PSA (tPSA) in human that could be used as alternative commercially available vitro diagnostic assays rely on mouse monoclonal IgG.A sandwich based anti-PSA IgY antibody was developed. ability detect free complexed at same molar ratio. The assay optimized, its analytical performance verified...
Abstract Neutrophils are a type of granulocyte important in the “first line defense” innate immune system. Upon activation, they facilitate destruction invading microorganisms by production superoxide radicals, as well release enzymatic contents their lysozymes. These enzymes include specific serine proteases: cathepsin G, neutrophil elastase, proteinase 3, recently discovered protease 4 (NSP4). Under normal conditions, proteolytic activity proteases is tightly regulated endogenous serpins;...
West Nile virus (WNV) is a member of the flavivirus genus belonging to Flaviviridae family. The viral serine protease NS2B/NS3 has been considered an attractive target for development anti-WNV agents. Although several inhibitors have described so far, most them are reversible inhibitors. Herein, we present series α-aminoalkylphosphonate diphenyl esters and their peptidyl derivatives as potent protease. inhibitor identified was Cbz-Lys-Arg-(4-GuPhe)P(OPh)2 displaying Ki k2/Ki values 0.4 µM 28...