ArticleACS medicinal chemistry letters2015
Synthesis and Evaluation of Conjugates of Novel TLR7 Inert Ligands as Self-Adjuvanting Immunopotentiators.
Article in ACS medicinal chemistry letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 12 citations in OpenAlex.
- A tractable covalent linker strategy for the production of immunogenic antigen-TLR7/8L bioconjugates.Chemical communications (Cambridge, England) · 2021Article
- The impact of immuno-aging on SARS-CoV-2 vaccine development.GeroScience · 2021Review
- Synthetic MUC1 breast cancer vaccine containing a Toll-like receptor 7 agonist exerts antitumor effects.Oncology letters · 2020Article
- Multifunctional Protein Conjugates with Built-in Adjuvant (Adjuvant-Protein-Antigen) as Cancer Vaccines Boost Potent Immune Responses.iScience · 2020Article
- Design and Synthesis of N1-Modified Imidazoquinoline Agonists for Selective Activation of Toll-like Receptors 7 and 8.ACS medicinal chemistry letters · 2017Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During the design and synthesis of a series of 8-hydroxy-2-(2-methoxyethoxy)-adenine derivatives bearing various substituted -RCOOH groups at the 9-position, we identified a TLR7-inert ligand, which does not activate TLR7 signaling pathway. Of interest, the coupling of weakly immunogenic antigens via the -RCOOH group was able to significantly enhance the immunogenicity of the antigens. Herein, an inert ligand, 9-(3-carboxypropyl)-8-hydroxy-2-(2-methoxyethoxy)-adenine (5, GD2), was synthesized and conjugated to 5 different weakly immunogenic antigens (BSA, OVA, MSA, MG7, and thymosin). Compared with the GD2 and the potent agonist UC-1 V150, all conjugates demonstrated potent immunogenicity in vitro and in vivo. All conjugates induced prolonged increases, while UC-1 V150 showed a rapid decline in the levels of proinflammatory cytokines following initial increases. These data indicate that the immunostimulatory activity of TLR7-inert ligands could be amplified and prolonged by conjugation to antigens, thus broadening the potential therapeutic application of these agents.
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