A5042134449- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Chemical Synthesis and Analysis
- Mosquito-borne diseases and control
- Genomics, phytochemicals, and oxidative stress
- interferon and immune responses
- Microbial Natural Products and Biosynthesis
- Eicosanoids and Hypertension Pharmacology
- Virus-based gene therapy research
- Synthetic Organic Chemistry Methods
- RNA and protein synthesis mechanisms
- Peroxisome Proliferator-Activated Receptors
- Click Chemistry and Applications
- Receptor Mechanisms and Signaling
- Plant Virus Research Studies
- Biochemical and Structural Characterization
- Cell Image Analysis Techniques
- Bacterial Genetics and Biotechnology
- Synthesis and biological activity
- Bacteriophages and microbial interactions
- Molecular Biology Techniques and Applications
- SARS-CoV-2 and COVID-19 Research
- Synthesis and Catalytic Reactions
- bioluminescence and chemiluminescence research
- Diatoms and Algae Research
Aarhus University
2018-2025
Abstract Antiviral strategies to inhibit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here, we demonstrate that NRF2 antioxidant gene expression pathway is suppressed in biopsies obtained from patients. Further, uncover agonists 4-octyl-itaconate (4-OI) clinically approved dimethyl fumarate (DMF) induce a cellular antiviral program potently inhibits replication SARS-CoV2 across cell lines. The inhibitory effect...
Abstract The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier clinical effectiveness, as resistance this treatment can occur through the inhibition viral spread within tumor, potentially leading failures. Here we show that 4-octyl itaconate (4-OI), chemical derivative Krebs cycle-derived metabolite itaconate, enhances with VSVΔ51 various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids...
Polyether ionophores are potent antimicrobials, albeit also cytotoxic against mammalian cells. We have identified several polyether containing a common hydro-2,2’-bifuran-2-ol (hemiketal) moiety, which cannot be derived from the canonical biosynthetic steps observed for compound class suggesting an unusual oxidative transformation. To identify responsible enzyme, we applied CRISPR-BEST to knock out genes in lysocellin-producing strain S. longwoodensis. This allowed us propose first...
The transcription factor BACH1 is a potential therapeutic target for variety of chronic conditions linked to oxidative stress and inflammation, as well cancer metastasis. However, only few degraders/inhibitors have been described. transcriptional repressor heme oxygenase 1 (HMOX1), which positively regulated by NRF2 highly inducible derivatives the synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO). Most activities these compounds are due their...
Isobenzopyrylium ions are unique, highly reactive, aromatic intermediates which largely unexplored in asymmetric catalysis despite their high potential synthetic utility. In this study, an organocatalytic multicomponent cascade via dienamine catalysis, involving a cycloaddition, nucleophilic addition, and ring-opening reaction, is disclosed. The reaction furnishes chiral tetrahydronaphthols containing four contiguous stereocenters good to yield, diastereoselectivity (up >20:1), excellent...
Electrophilic groups are one of the key pillars contemporary chemical biology and medicinal chemistry. For instance, 3-membered N-heterocyclic compounds-such as aziridines, azirines, oxaziridines-possess unique electronic structural properties which underlie their potential applicability covalent tools. The α-lactams also members this group compounds, however, utility within field remains unexplored. Here, we demonstrate an α-lactam reagent (AM2) that is tolerant to aqueous buffers while...
The development of new immunomodulatory agents can impact various areas medicine. In particular, compounds with the ability to modulate innate immunological pathways hold significant unexplored potential. Herein, we report a modular synthetic approach macrodiolide natural product (-)-vermiculine, an agent previously shown possess diverse biological effects, including cytotoxic and immunosuppressive activity. synthesis allows for high degree flexibility in modifying macrocyclic framework,...
The natural products pantomycin and stendomycin were both reported as antimicrobial agents. We demonstrate by gene cluster analysis, LC–MS isolation that these polypeptides are identical, we identify previously unknown congeners. show can be chemically modified at its electrophilic dehydrobutyrine moiety yielding the first bioactive analogue of this product which undergo additional functionalization. This compound may a valuable starting point for molecular probe development, invite...
The polyether ionophores are complex natural products capable of transporting cations across biological membranes. Many family members possess highly potent antimicrobial activity and a few selected compounds have ability to target particularly aggressive cancer cells. Despite these interesting perspectives, detailed understanding the cellular mode-of-action is generally lacking. In principle, broad mapping structure-activity relationships several activities could provide mechanistic...
Abstract Carboxylic polyether ionophores (CPIs) are among the most prevalent agricultural antibiotics (notably in US) and these compounds have been use for decades. The potential to reposition CPIs beyond veterinary use, e. g. through chemical modifications enhance their selectivity window, is an exciting challenge opportunity, considering general resilience towards resistance development. Given very large societal impact of somewhat controversial compounds, it surprising that many aspects...
Abstract A novel cascade reaction initiated by an enantioselective aminocatalysed 1,3‐dipolar [6+4] cycloaddition between catalytically generated trienamines and 3‐oxidopyridinium betaines is presented. The cycloadduct spontaneously undergoes intramolecular enamine‐mediated aldol, hydrolysis, E1cb sequence, which ultimately affords a chiral hexahydroazulene framework. In this process, three new C−C bonds stereocenters are formed, enabled formal unfolding of the pyridine moiety from dipolar...
Abstract A novel strategy that combines oxidative aminocatalysis and gold catalysis allows the preparation of chiral α‐quaternary isochromanes, a motif is prevalent in natural products synthetic bioactive compounds. In first step, α‐branched aldehydes propargylic alcohols are transformed into ethers with excellent optical purities (>90 % ee ) via umpolung DDQ an amino acid‐derived primary amine catalyst. Subsequent gold(I)‐catalyzed intramolecular hydroarylation affords isochromane...
The oxidation status of N-terminal cysteines directly dictates protein stability via arginylation and proteasomal degradation. However, only a handful proteins have been shown to be regulated this pathway. To date, no methods detect cysteine reactivity abundance has reported. Here, we demonstrate, for the first time, that targeting probes can used in living cells bind quantify cysteines, discriminating their state. Using these probes, identify hundreds show changes under hypoxia detected. We...
The polyether ionophores are complex natural products capable of transporting cations across biological membranes. Many family members possess highly potent antimicrobial activity and a few selected compounds have ability to target particularly aggressive cancer cells. Despite these interesting perspectives, detailed understanding the cellular mode-of-action is generally lacking. In principle, broad mapping structure-activity relationships several activities could provide mechanistic...
Abstract Antiviral strategies to inhibit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here we demonstrate that NRF2 anti-oxidant gene expression pathway is suppressed in biopsies obtained from patients. Further, uncover agonists 4-octyl-itaconate (4-OI) clinically approved dimethyl fumarate (DMF) induce a cellular anti-viral program, which potently inhibits replication SARS-CoV2 across cell lines. The program...
Covalently acting compounds experience a strong interest within chemical biology both as molecular probes in studies of fundamental biological mechanisms and/or novel drug candidates. In this context, the identification new classes reactive groups is particularly important these can expose reactivity modes and, consequently, expand ligandable proteome. Here, we investigated electrophilic 3-acyl-5-hydroxy-1,5-dihydro-2H-pyrrole-2-one (AHPO) scaffold, heterocyclic motif that e.g. present...
Abstract Pandemic spread of emerging human pathogenic viruses such as the current SARS-CoV-2, poses both an immediate and future challenge to health society. Currently, effective treatment infection with SARS-CoV-2 is limited broad spectrum antiviral therapies meet other pandemics are absent leaving World population largely unprotected. Here, we have identified distinct members family polyether ionophore antibiotics potent ability inhibit replication cytopathogenicity in cells. Several...
Abstract Electrophilic groups are one of the key pillars contemporary chemical biology and medicinal chemistry. For instance, 3‐membered N ‐heterocyclic compounds—such as aziridines, azirines, oxaziridines—possess unique electronic structural properties which underlie their potential applicability covalent tools. The α‐lactams also members this group compounds, however, utility within field remains unexplored. Here, we demonstrate an α‐lactam reagent ( AM2 ) that is tolerant to aqueous...