engleski

Design, synthesis and evaluation of immunostimulating activities of mannosylated desmuramyl peptides containing lipophilic substituents

Muramyl dipeptide (MDP, N-acetylmuramyl-L-alanyl- D-isoglutamine) is the smallest peptidoglycan fragment capable to trigger the immune response. MDP acts as a pathogen-associated molecular pattern and activates the NOD2 (Nucleotide Binding Oligomerization Domain Containing 2) receptor. The main parameter for the improvement of its pharmacological properties is lipophilicity. Up to now, our research was directed towards desmuramyl peptides containing adamantane and their mannose derivatives. Namely, mannose receptors presented on immunocompetent cells are considered to be pattern-recognition receptors, as well as NOD2, and therefore they can affect the immune reactions. Here we present the design and synthesis of mannosylated desmuramyl peptides containing lipophilic substituents attached at D- isoglutamine/D-glutamic acid of dipeptide pharmacophore through 1, 2, 3-triazole moiety. Their immunostimulating activities are evaluated in vivo in the mouse model using ovalbumin as an antigen. Lipophilic substituents attached over α- COOH of D- Glu contribute to the immunostimulation while the presence of free γ-COOH at D-Glu/D- isoGln is important for establishing interactions with native receptor.

desmuramyl peptide, mannose , immunostimulation

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