engleski

Design, Synthesis and Evaluation of Immunostimulating Activities of Desmuramyl Peptides Containing 2- Aminoadamantane-2-carboxylic Acid

Muramyl dipeptide (MDP, N-acetylmuramyl-L-alanyl- D-isoglutamine) is the smallest peptidoglycan fragment capable of replacing the whole Mycobacteria in Freund’s adjuvant. MDP acts as a pathogen-associated molecular pattern and activates the NOD2 receptor. Numerous structural variations of MDP have been performed in order to improve its pharmacological properties. The main parameter for the improvement is lipophilicity. We have designed and prepared desmuramyl peptides containing lypophilic 2-aminoadamantane-2- carboxylic acid, and furthermore modified it with mannose moieties. 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 synthesis and biological evaluation of desmuramyl peptides containing 2- aminoadamantane-2-carboxylic acid, and its mono- and di-mannosylated derivatives. Their immunostimulating activities were evaluated in vivo in the mouse model using ovalbumin as an antigen. The effects on the secondary humoral response were determined by measuring overall anti-OVA IgG antibodies, and the subclasses anti- OVA IgG1 and anti-OVA IgG2a. Mannosylated desmuramyl peptides exhibited an improved immunological activity and the di-mannoslyated derivative showed to be the most active one.

Desmuramyl Peptide ; 2-Aminoadamantane-2-carboxylic Acid ; Immunostimulating Activity

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