AI Article Synopsis
- Researchers are focusing on creating new immune boosters that trigger cellular immune responses by using two specific immune receptors, NOD2 and TLR7, together.
- The study explores how different chemical linkers impact the effectiveness and solubility of these immune-activating compounds, showing they can significantly enhance immune responses in human immune cells.
- Findings suggest that the design of these compounds can be optimized for better immune activation, contributing valuable knowledge for future immune booster development.
Article Abstract
There is a growing interest in developing novel immune potentiators capable of eliciting a cellular immune response. We tackle this challenge by harnessing the synergistic cross-activation between two innate immune receptors─the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and Toll-like receptor 7 (TLR7). Herein, we investigate the structure-activity relationship of a series of novel conjugated NOD2/TLR7 agonists incorporating a variety of flexible aliphatic, poly(ethylene glycol)-based and triazole-featuring linkers. Our findings reveal potent immune-enhancing properties of conjugates in human primary peripheral blood mononuclear cells, characterized by a Th1/Th17 polarized cytokine response. Importantly, we demonstrate that both the chemistry of the linker and the site of linkage affect the immune fingerprint and the kinetic solubility of these conjugated agonists. These results shed further light on the immunostimulatory potential of NOD2/TLR7 cross-activation and provide insights for designing innovative immune potentiators.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583123 | PMC |
| http://dx.doi.org/10.1021/acs.bioconjchem.4c00321 | DOI Listing |
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