20.500.12556/RUL-165195 Linker chemistry and connectivity fine-tune the immune response and kinetic solubility of conjugated NOD2/TLR7 agonists 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. agonists amines conjugate acid-base pairs peptides proteins solubility agonisti amini konjugirani kislinsko-bazični pari peptidi proteini topnost imunski odziv farmacevtska kemija true false true Angleški jezik Slovenski jezik Članek v reviji 2024-11-26 14:46:40 2024-11-26 14:46:43 2024-11-27 03:50:49 0000-00-00 00:00:00 2024 0 0 Str. 1723–1731 iss. 11 Vol. 35 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.4:54:616.097 1520-4812 10.1021/acs.bioconjchem.4c00321 211169539 janez-et-al-2024-linker-chemistry-and-connectivity-fine-tune-the-immune-response-and-kinetic-solubility-of-conjugated.pdf janez-et-al-2024-linker-chemistry-and-connectivity-fine-tune-the-immune-response-and-kinetic-solubility-of-conjugated.pdf 1 F787A8DFD2172C9E29F5B0FCB237BE63 0f2d49d9b7d78ac3e6f4b3f7d00e55c9cf4f851945623e48ee7777daf451fdc6 b0e046f3-abfc-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=196215 https://pubs.acs.org/doi/10.1021/acs.bioconjchem.4c00321 1 7627edf6-abfc-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=196213 Fakulteta za farmacijo 0 0 0