Linker Chemistry and Connectivity Fine-Tune the Immune Response and Kinetic Solubility of Conjugated NOD2/TLR7 Agonists.

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 th

SUBMITTER: Janez S 

PROVIDER: S-EPMC11583123 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature