Distinctive Immune Signatures Driven by Structural Alterations in Desmuramylpeptide NOD2 Agonists.

ABSTRACT: 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 (EC₅₀ = 4.6 nM), exhibiting an almost 17-fold enhancement in potency compared to its unsubstituted counterpart 1 (EC₅₀ = 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

SUBMITTER: Janez S 

PROVIDER: S-EPMC11472310 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature