A5066709244- Receptor Mechanisms and Signaling
- Protein Structure and Dynamics
- COVID-19 Clinical Research Studies
- Regulation of Appetite and Obesity
- SARS-CoV-2 and COVID-19 Research
- Adipokines, Inflammation, and Metabolic Diseases
- Adipose Tissue and Metabolism
- Neuropeptides and Animal Physiology
- Long-Term Effects of COVID-19
King's College London
2022-2024
University of Copenhagen
2019-2020
Novo Nordisk Foundation
2019-2020
Significance Structures of G protein-coupled receptors (GPCRs) in complex with ligands mainly provide frozen pictures little information about the actual molecular mechanism action ligand normally highly dynamic receptor. Through computer-based dynamics simulations a receptor for long-chain fatty acids, free acid 1 (FFAR1), we discover that an unoccupied, solvent-exposed pocket closes on removal lipid-like agonist; is, during major conformational change Importantly, compound designed to...
Long-chain fatty acids (LCFAs) released from adipocytes inhibit lipolysis through an unclear mechanism. We hypothesized that the LCFA receptor, FFAR4 (GPR120), which is highly expressed in adipocytes, may be involved this feedback regulation. Liquid chromatography mass spectrometry (LC-MS) analysis of conditioned media isoproterenol-stimulated primary cultures murine and human demonstrated most non-esterified free (NEFAs) are known agonists for FFAR4. In agreement with this, medium...
The free fatty acid receptors FFAR1 and FFAR4 are considered promising therapeutic targets for management of metabolic inflammatory diseases. However, there is a need entirely novel chemical scaffolds, since many the highly similar lipophilic chemotypes in development have been abandoned by pharmaceutical industry, due to toxic effects on hepatocytes β-cells. Our group has recently reported discovery 1,3,5-triazine-2-amine-based compound that acts as an allosteric agonist FFAR1. Here, we...
The role of myeloid cells in the pathogenesis SARS-CoV-2 is well established, particular as drivers cytokine production and systemic inflammation characteristic severe COVID-19. However, potential for to act bona fide targets productive infection, specifics entry, remain unclear. Using a panel anti-SARS-CoV-2 monoclonal antibodies (mAbs) we performed detailed assessment antibody-mediated infection monocytes/macrophages. mAbs with most consistent mediate were those targeting conserved region...