Academic Journal

Receptor–Ligand Kinetics Influence the Mechanism of Action of Covalently Linked TLR Ligands

التفاصيل البيبلوغرافية
العنوان: Receptor–Ligand Kinetics Influence the Mechanism of Action of Covalently Linked TLR Ligands
المؤلفون: Flora W. Kimani (10065325), Jainu Ajit (10065328), Alexander Galluppi (10065331), Saikat Manna (1583338), William J. Howitz (5473595), Sophia Tang (10065334), Aaron P. Esser-Kahn (1247058)
سنة النشر: 2021
المجموعة: Smithsonian Institution: Digital Repository
مصطلحات موضوعية: Biophysics, Biochemistry, Medicine, Cell Biology, Molecular Biology, Pharmacology, Biotechnology, Immunology, Infectious Diseases, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, B cells, cytokine expression profiles, receptor locations, TLR agonists, agonist influence, NF -κB, cell-based assays, time-resolved TNF -α, factor kappa-light-chain-enhancer, Toll-like receptor, TLR Ligands, activation kinetics, TLR systems, vaccine design, ligand specificity, Tumor Necrosis Factor
الوصف: We report a mechanistic study comparing the immune activation of conjugated Toll-like receptor (TLR) agonists and their unlinked mixtures. Herein, we synthesized a set of six linked dual agonists with different ligands, molecular structures, receptor locations, and biophysical characteristics. With these dimers, we ran a series of in vitro cell-based assays, comparing initial and overall NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation, cytokine expression profiles, as well as time-resolved TNF-α (Tumor Necrosis Factor alpha) expression. We show that initial activation kinetics, ligand specificity, and the dose of the agonist influence the activity of these linked TLR systems. These results can help improve vaccine design by showing how linked TLR agonists can improve their potency with the appropriate selection of key criteria.
نوع الوثيقة: article in journal/newspaper
اللغة: unknown
Relation: https://figshare.com/articles/journal_contribution/Receptor_Ligand_Kinetics_Influence_the_Mechanism_of_Action_of_Covalently_Linked_TLR_Ligands/13681774
DOI: 10.1021/acschembio.0c00924.s001
الاتاحة: https://doi.org/10.1021/acschembio.0c00924.s001
Rights: CC BY-NC 4.0
رقم الانضمام: edsbas.8E0E1339
قاعدة البيانات: BASE
الوصف
DOI:10.1021/acschembio.0c00924.s001