A5068994292- Peptidase Inhibition and Analysis
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Click Chemistry and Applications
- Protease and Inhibitor Mechanisms
- Chemical Synthesis and Analysis
- Malaria Research and Control
- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Cancer, Stress, Anesthesia, and Immune Response
- Parasites and Host Interactions
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Parasite Biology and Host Interactions
- Mycotoxins in Agriculture and Food
- Cell Adhesion Molecules Research
- Viral Infectious Diseases and Gene Expression in Insects
- HIV/AIDS drug development and treatment
- Blood Coagulation and Thrombosis Mechanisms
- Protein Degradation and Inhibitors
- Fungal Biology and Applications
- Microbial Natural Products and Biosynthesis
- Biochemical and Structural Characterization
Johannes Gutenberg University Mainz
2020-2024
Cornell University
2024
Weill Cornell Medicine
2024
Molecular Innovations (United States)
2024
Rhodesain is a major cysteine protease of Trypanosoma brucei rhodesiense, pathogen causing Human African Trypanosomiasis, and validated drug target. Recently, we reported the development α-halovinylsulfones as new class covalent reversible inhibitors. Here, α-fluorovinylsulfones/-sulfonates were optimized for rhodesain based on molecular modeling approaches. 2d, most potent selective inhibitor in series, shows single-digit nanomolar affinity high selectivity toward mammalian cathepsins B L....
In this study, we have identified and optimized two lead structures from an in-house screening, with promising results against the parasitic flatworm Schistosoma mansoni its target protease S. cathepsin B1 (SmCB1). Our correlation analysis highlighted significance of physicochemical properties for compounds' in vitro activities, resulting a dual approach to optimize structures, regarding both phenotypic effects newly transformed schistosomula (NTS), adult worms, SmCB1 inhibition. The...
Abstract The implementation of single‐use technologies offers several major advantages, e.g. prevention cross‐contamination, especially when spore‐forming microorganisms are present. This study investigated the application a bioreactor in batch fermentation filamentous fungus Penicillium sp. (IBWF 040‐09) from Institute Biotechnology and Drug Research (IBWF), which is capable intracellular production protease inhibitor against parasitic proteases as secondary metabolite. Several...
The cysteine protease cathepsin S (CatS) is overexpressed in many tumors. It known to be involved tumor progression as well antigen processing antigen-presenting cells (APC). Recent evidence suggests that silencing CatS improves the anti-tumor immune response several cancers. Therefore, an interesting target modulate these diseases. Here, we present a series of covalent-reversible inhibitors based on α-fluorovinylsulfone and -sulfonate warheads. We optimized two lead structures by molecular...
Fluorometric assays are one of the most frequently used methods in medicinal chemistry. Over last 50 years, reporter molecules for detection protease activity have evolved from first-generation colorimetric p-nitroanilides, through FRET substrates, and 7-amino-4-methyl coumarin (AMC)-based substrates. The aim further substrate development is to increase sensitivity reduce vulnerability assay interferences. Herein, we describe a new generation substrates based on...
Protease inhibitors represent a promising therapeutic option for the treatment of parasitic diseases such as malaria and human African trypanosomiasis. Falcitidin was first member new class falcipain-2, cysteine protease parasite Plasmodium falciparum. Using metabolomics dataset 25 Chitinophaga strains molecular networking enabled identification over 30 natural analogues falcitidin. Based on MS/MS spectra, they vary in their amino acid chain length, sequence, acyl residue, C-terminal...
ABSTRACT Herein, we performed a virtual screening study to discover new scaffolds for small molecule-based ligands of the immune checkpoint lymphocyte-activation gene 3 (LAG-3). Molecular dynamics (MD) simulations using LAG-3 structure revealed two putative binding sites molecules: antibody interface and lipophilic canyon. A 3D pharmacophore resulted in identification potential these afforded library 25 compounds. We then evaluated hits via microscale thermophoresis (MST) surface plasmon...
Herein, we performed a virtual screening study to discover new scaffolds for small molecule-based ligands of the immune checkpoint lymphocyte-activation gene 3 (LAG-3). Molecular dynamics (MD) simulations using LAG-3 structure revealed two putative binding sites molecules: antibody interface and lipophilic canyon. A 3D pharmacophore resulted in identification potential these afforded library 25 compounds. We then evaluated hits via microscale thermophoresis (MST) surface plasmon resonance...
Cathepsin S (catS) is a member of the cysteine protease family with limited tissue distribution, which predominantly found in antigen-presenting cells. Due to overexpression and overactivity catS numerous cancers, inhibition supposed improve antitumor response. Here, we explore potential small-molecule inhibitors emphasizing their vitro pharmacodynamics pharmacokinetics. Membrane permeability selected was measured Parallel Artificial Permeation Assay correlated calculated physicochemical...
ABSTRACT Protease inhibitors represent a promising therapeutic option for the treatment of parasitic diseases such as malaria and human African trypanosomiasis. Falcitidin was first member new class falcipain-2, cysteine protease parasite Plasmodium falciparum . Using metabolomics dataset 25 Chitinophaga strains molecular networking enabled identification over 30 natural analogs falcitidin. Based on MS/MS spectra, they vary in their amino acid chain length, sequence, acyl residue, C...