20.500.12556/RUL-163778 Distinctive immune signatures driven by structural alterations in desmuramylpeptide NOD2 agonists Herein we report on the design, synthesis and biological evaluation of a series of nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) desmuramylpeptide agonists. The structural prerequisites that shape both physicochemical and immunomodulatory profiles of desmuramylpeptide NOD2 agonists have been delineated. Within this context, we identified 3, a butyrylated desmuramylpeptide, as a potent in vitro NOD2 agonist (EC$_{50}$ = 4.6 nM), exhibiting an almost 17-fold enhancement in potency compared to its unsubstituted counterpart 1 (EC$_{50}$ = 77.0 nM). The novel set of desmuramylpeptides demonstrate unique in vitro immunomodulatory activities. They elicited cytokine production in peripheral blood mononuclear cells (PBMCs), both alone and in conjunction with lipopolysaccharide (LPS). The spermine-decorated 32 also stimulated the LPS-induced cytotoxic activity (2.95-fold) of PBMCs against K562 cancer cells. Notably, the cholesterol-conjugate 26 displayed anti-inflammatory actions, highlighted by its capacity to convert the inflammatory monocyte subset into an anti-inflammatory phenotype. Finally, the eicosapentaenoylated derivative 23 augmented antigen presentation by mouse bone marrow-derived dendritic cells (BMDCs), thus highlighting its potential as a vaccine adjuvant. agonists cells peptides proteins reaction products toxicity agonisti celice peptidi in proteini reakcijski produkti toksičnost imunomodulatorji true false true Angleški jezik Slovenski jezik Članek v reviji 2024-10-10 13:52:17 2024-10-10 13:52:23 2024-10-12 03:55:07 0000-00-00 00:00:00 2024 0 0 Str. 17585–17607 iss. 19 Vol. 67 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.9+615.375 1520-4804 10.1021/acs.jmedchem.4c01577 209432835 janez-et-al-2024-distinctive-immune-signatures-driven-by-structural-alterations-in-desmuramylpeptide-nod2-agonists_(1).pdf janez-et-al-2024-distinctive-immune-signatures-driven-by-structural-alterations-in-desmuramylpeptide-nod2-agonists_(1).pdf 1 9755E7D8071353759D9507AA4F6447D7 6d12e66b089a788e6900bf2dbd08cb49ba241a9f62f4cf0f31c84917ed24fc84 9c63d585-86fe-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=193699 https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c01577 1 eded73f7-86fd-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=193698 Fakulteta za farmacijo 0 0 0