A5061572826- Peptidase Inhibition and Analysis
- vaccines and immunoinformatics approaches
- Pneumocystis jirovecii pneumonia detection and treatment
- Autoimmune and Inflammatory Disorders Research
- Neuropeptides and Animal Physiology
- Inflammasome and immune disorders
- Galectins and Cancer Biology
- Pneumonia and Respiratory Infections
- SARS-CoV-2 and COVID-19 Research
- Biochemical and Structural Characterization
- Immunotherapy and Immune Responses
- Spondyloarthritis Studies and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Ubiquitin and proteasome pathways
- Antifungal resistance and susceptibility
- Protease and Inhibitor Mechanisms
National Centre of Scientific Research "Demokritos"
2020-2024
University of Patras
2020-2023
Polymorphic variation of immune system proteins can drive variability individual responses. Endoplasmic reticulum aminopeptidase 1 (ERAP1) generates antigenic peptides for presentation by major histocompatibility complex class I molecules. Coding SNPs in ERAP1 have been associated with predisposition to inflammatory rheumatic disease and shown affect functional properties the enzyme, but interplay between combinations these as they exist allotypes has not thoroughly explored. We used phased...
The oxytocinase subfamily of M1 zinc aminopeptidases comprises emerging drug targets, including the ER-resident 1 and 2 (ERAP1 ERAP2) insulin-regulated aminopeptidase (IRAP); however, reports on clinically relevant inhibitors are limited. Here we report a new synthetic approach high diastereo- regioselectivity for functionalization α-hydroxy-β-amino acid scaffold bestatin. Stereochemistry mechanism inhibition were investigated by high-resolution X-ray crystal structure ERAP1 in complex with...
Recent studies have linked the activity of ER aminopeptidase 2 (ERAP2) to increased efficacy immune-checkpoint inhibitor cancer immunotherapy, suggesting that pharmacological inhibition ERAP2 could important therapeutic implications. To explore effects on immunopeptidome cells, we treated MOLT-4 T lymphoblast leukemia cells with a recently developed selective inhibitor, isolated Major Histocompatibility class I molecules (MHCI), and sequenced bound peptides by liquid chromatography tandem...
ER aminopeptidase 1 (ERAP1) is an ER-resident that excises N-terminal residues of peptides then bind onto Major Histocompatibility Complex I molecules (MHC-I) and indirectly modulates adaptive immune responses. ERAP1 contains allosteric regulatory site accommodates the C-terminus at least some peptide substrates, raising questions about its exact influence on antigen presentation potential inhibition for cancer immunotherapy. We used inhibitor targets this to study effect immunopeptidome a...
Insulin-Regulated aminopeptidase (IRAP) is a zinc-dependent with several important biological functions and an emerging pharmaceutical target for cognitive enhancement immune system regulation. Aiming to discover lead-like IRAP inhibitors enhanced selectivity versus homologous enzymes, we targeted allosteric site at the C-terminal domain pocket of IRAP. We compiled library 2.5 million commercially available compounds from ZINC database, performed molecular docking corresponding endoplasmic...
Population genetic variability in immune system genes can often underlie responses to pathogens. Cytotoxic T-lymphocytes are emerging as critical determinants of both severe acute respiratory syndrome coronavirus 2 infection severity and long-term immunity, after either recovery or vaccination. A hallmark disease 2019 is its highly variable breadth between individuals. To address the underlying mechanisms behind this phenomenon, we analyzed proteolytic processing S1 spike glycoprotein...
Endoplasmic reticulum aminopeptidase 1 (ERAP1) cleaves the N-terminal amino acids of peptides, which can then bind onto major histocompatibility class I (MHC-I) molecules for presentation cell surface, driving activation adaptive immune responses. In cancer, overtrimming mature antigenic peptides reduce cytotoxic T-cell responses, and ERAP1 generate self-antigenic contribute to autoimmune cellular Therefore, modulation activity has potential therapeutic indications cancer immunotherapy in...
ABSTRACT Population genetic variability in immune system genes can often underlie responses to pathogens. Cytotoxic T-lymphocytes are emerging as critical determinants of both SARS-CoV-2 infection severity and long-term immunity, either after recovery or vaccination. A hallmark COVID-19 is its highly variable breadth between individuals. To address the underlying mechanisms behind this phenomenon we analyzed proteolytic processing S1 spike glycoprotein precursor antigenic peptides by 10...
Abstract ER aminopeptidase 1 (ERAP1) is an ER-resident that excises N-terminal residues off peptides then bind onto Major Histocompatibility Complex I molecules (MHC-I) and indirectly modulates adaptive immune responses. ERAP1 contains allosteric regulatory site accommodates the C-terminus of at least some peptide substrates, raising questions about its exact influence on antigen presentation potential inhibition for cancer immunotherapy. We used inhibitor targets this to study effect...
Abstract Objective Polymorphic variation of immune system proteins can drive variability individual responses. ER aminopeptidase 1 (ERAP1) generates antigenic peptides for presentation by MHC class I molecules. Coding single nucleotide polymorphisms (SNPs) in ERAP1 have been associated with predisposition to inflammatory rheumatic disease and shown affect functional properties the enzyme, but interplay between combinations these SNPs as they exist allotypes, has not thoroughly explored....
Insulin-regulated aminopeptidase is a zinc-dependent with several important biological functions and an emerging pharmaceutical target for cognitive enhancement immune system regulation. Aiming to discover lead-like IRAP inhibitors enhanced selectivity versus homologous enzymes, we chose allosteric site at the C-terminal domain pocket of IRAP. We compiled library 2.6 million commercially available compounds from ZINC database, MW 200–350, cLogP <3.0 lacking reactive groups or PAINS. This was...