ArticleBioconjugate chemistry2011
Synthesis and characterization of PEGylated toll like receptor 7 ligands.
Article in Bioconjugate chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Endocytosis-independent cytosolic entry of messenger RNA via fluorous bilayer zippering attenuating Toll-like receptor signaling and enables ischemic tissue salvage.Smart molecules : open access · 2026Article
- TLR Agonists Delivered by Plant Virus and Bacteriophage Nanoparticles for Cancer Immunotherapy.Bioconjugate chemistry · 2023Article
- Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants.Advanced drug delivery reviews · 2021Review
- A tractable covalent linker strategy for the production of immunogenic antigen-TLR7/8L bioconjugates.Chemical communications (Cambridge, England) · 2021Article
- Oral administration of PEGylated TLR7 ligand ameliorates alcohol-associated liver disease via the induction of IL-22.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Synthetic Toll-like Receptors 7 and 8 Agonists: Structure-Activity Relationship in the Oxoadenine Series.ACS omega · 2019Article
- High potency of lipid conjugated TLR7 agonist requires nanoparticulate or liposomal formulation.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2018Article
- Toll-like Receptor Agonist Conjugation: A Chemical Perspective.Bioconjugate chemistry · 2018Review
- Article
- Synthetic Toll-Like Receptor 4 (TLR4) and TLR7 Ligands Work Additively via MyD88 To Induce Protective Antiviral Immunity in Mice.Journal of virology · 2017Article
- Strategies for designing synthetic immune agonists.Immunology · 2016Review
- Potential of PEGylated Toll-Like Receptor 7 Ligands for Controlling Inflammation and Functional Changes in Mouse Models of Asthma and Silicosis.Frontiers in immunology · 2016Article
- A conjugate of octamer-binding transcription factor 4 and toll-like receptor 7 agonist prevents the growth and metastasis of testis embryonic carcinoma.Journal of translational medicine · 2015Article
- Induction of Tolerogenic Dendritic Cells by a PEGylated TLR7 Ligand for Treatment of Type 1 Diabetes.PloS one · 2015Article
- Directing the immune system with chemical compounds.ACS chemical biology · 2014Review
- Review
- Treatment of autoimmune inflammation by a TLR7 ligand regulating the innate immune system.PloS one · 2012Article
- Mast cell-mediated inhibition of abdominal neutrophil inflammation by a PEGylated TLR7 ligand.Mediators of inflammation · 2012Article
- Inhibition of keratinocyte proliferation by phospholipid-conjugates of a TLR7 ligand in a Myc-induced hyperplastic actinic keratosis model in the absence of systemic side effects.European journal of dermatology : EJDArticle
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Toll-like receptor 7 (TLR7) is located in the endosomal compartment of immune cells. Signaling through TLR7, mediated by the adaptor protein MyD88, stimulates the innate immune system and shapes adaptive immune responses. Previously, we characterized TLR7 ligands conjugated to protein, lipid, or poly(ethylene glycol) (PEG). Among the TLR7 ligand conjugates, the addition of PEG chains reduced the agonistic potency. PEGs are safe in humans and widely used for improvement of pharmacokinetics in existing biologics and some low molecular weight compounds. PEGylation could be a feasible method to alter the pharmacokinetics and pharmacodynamics of TLR7 ligands. In this study, we systematically studied the influence of PEG chain length on the in vitro and in vivo properties of potent TLR7 ligands. PEGylation increased solubility of the TLR7 ligands and modulated protein binding. Adding a 6-10 length PEG to the TLR7 ligand reduced its potency toward induction of interleukin (IL)-6 by murine macrophages in vitro and IL-6 and tumor necrosis factor (TNF) in vivo. However, PEGylation with 18 or longer chain restored, and even enhanced, the agonistic activity of the drug. In human peripheral blood mononuclear cells, similar effects of PEGylation were observed for secretion of proinflammatory cytokines, IL-6, IL-12, TNF-α, IL-1β, and type 1 interferon, as well as for B cell proliferation. In summary, these studies demonstrate that conjugation of PEG chains to a synthetic TLR ligand can impact its potency for cytokine induction depending on the size of the PEG moiety. Thus, PEGylation may be a feasible approach to regulate the pharmacological properties of TLR7 ligands.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.