A5023747241- Microbial Natural Products and Biosynthesis
- Antibiotic Resistance in Bacteria
- Ubiquitin and proteasome pathways
- Antimicrobial Peptides and Activities
- Glycosylation and Glycoproteins Research
- Biochemical and Structural Characterization
- Cancer therapeutics and mechanisms
- Carbohydrate Chemistry and Synthesis
- Peroxisome Proliferator-Activated Receptors
- Monoclonal and Polyclonal Antibodies Research
- Traditional and Medicinal Uses of Annonaceae
- Antibiotic Use and Resistance
- Pancreatic function and diabetes
- Endoplasmic Reticulum Stress and Disease
- Peptidase Inhibition and Analysis
- Cannabis and Cannabinoid Research
- Genomics and Phylogenetic Studies
Leiden University
2019-2024
Oncode Institute
2020
Mammalian genomes encode seven catalytic proteasome subunits, namely, β1c, β2c, β5c (assembled into constitutive 20S core particles), β1i, β2i, β5i (incorporated immunoproteasomes), and the thymoproteasome-specific subunit β5t. Extensive research in past decades has yielded numerous potent inhibitors including compounds currently used clinic to treat multiple myeloma mantle cell lymphoma. Proteasome that selectively target combinations of β1c/β1i, β2c/β2i, or β5c/β5i are available, yet...
Brevicidine and laterocidine are two recently discovered lipopeptide antibiotics with promising antibacterial activity. Possessing a macrocyclic core, multiple positive charges, lipidated N-terminus, these lipopeptides exhibit potent selective activity against Gram-negative pathogens, including polymyxin-resistant isolates. Given the low amounts of brevicidine accessible by fermentation producing microorganisms, synthetic routes to present an attractive alternative. We here report convenient...
Brevicidine and laterocidine are macrocyclic lipodepsipeptides with selective activity against Gram-negative bacteria, including colistin-resistant strains. Previously, the core of these peptides was thought essential for antibacterial activity. In this study, we show that C-terminal amidation linear brevicidine scaffolds, substitution native Thr9, yields analogues retain potent low hemolysis parent compounds. Furthermore, an alanine scan both revealed aromatic basic amino acids within...
The brevicidine and laterocidine family of lipopeptide antibiotics exhibit strong activity against multidrug-resistant Gram-negative bacteria, while showing low propensity to induce resistance. Both peptides feature a branched lipid tail on the N-terminal residue, which for is chiral. Here, we report synthesis biological evaluation library analogues wherein replaced with linear achiral fatty acids. Optimal chain lengths were determined new colistin-resistant E. coli produced.
The phospholipase A and acyltransferase (PLAAT) family of cysteine hydrolases consists five members, which are involved in the Ca2+-independent production N-acylphosphatidylethanolamines (NAPEs). NAPEs lipid precursors for bioactive N-acylethanolamines (NAEs) that various physiological processes such as food intake, pain, inflammation, stress, anxiety. Recently, we identified α-ketoamides first pan-active PLAAT inhibitor scaffold reduced arachidonic acid levels PLAAT3-overexpressing U2OS...
The prevalence of multidrug-resistant (MDR) pathogens combined with a decline in antibiotic discovery presents major challenge for health care. To refill the pipeline, we need to find new ways uncover chemical entities. Here, report global genome mining-guided lipopeptide antibiotics tridecaptin A5 and D, which exhibit unusual bioactivities within their class. change antibacterial spectrum Oct-TriA5 was explained solely by Phe Trp substitution as compared Oct-TriA1, while Oct-TriD contained...
Brevicidine and laterocidine are two recently discovered lipopeptide antibiotics with promising antibacterial activity. Possessing a macrocyclic core, multiple positive charges, lipidated N -terminus, these lipopeptides exhibit potent selective activity against Gram-negative pathogens including polymyxin-resistant isolates. Given the low amounts of brevicidine accessible by fermentation producing microorganisms, synthetic routes to present an attractive alternative. We here report convenient...
Brevicidine and laterocidine are two recently discovered lipopeptide antibiotics with promising antibacterial activity. Possessing a macrocyclic core, multiple positive charges, lipidated <i>N</i>-terminus, these lipopeptides exhibit potent selective activity against Gram-negative pathogens including polymyxin-resistant isolates. Given the low amounts of brevicidine accessible by fermentation producing microorganisms, synthetic routes to present an attractive alternative. We here...
Brevicidine and laterocidine are two recently discovered lipopeptide antibiotics with promising antibacterial activity. Possessing a macrocyclic core, multiple positive charges, lipidated N-terminus, these lipopeptides exhibit potent selective activity against Gram-negative pathogens, including polymyxin-resistant isolates. Given the low amounts of brevicidine accessible by fermentation producing microorganisms, synthetic routes to present an attractive alternative. We here report convenient...