engleski

Adamantane-containing desmuramyl peptides: synthesis and structural insight into NOD2 binding

Muramyl dipeptide (MDP, N-acetylmuramyl-L-alanyl- D-isoglutamine) is a conserved fragment of a bacterial cell walls and the smallest peptidoglycan fragment competent to trigger the immune response. MDP binds to NOD2 (nucleotide binding and oligomerization domain-containing protein 2) with affinity in the nanomolar range. Activation of NOD2 by MDP stimulates downstream signaling pathways and promote immune responses. Minor MDP structure modifications affect molecular recognition by NOD2, and thereby influence the modulation of the immune response. Here we present the synthesis of MDP analogs, desmuramyl peptides (DMPs) with incorporated lipophilic adamantly groups at the N-terminus of the dipeptide pharmacophore. The adamantly group was introduced in two ways, via 2-aminoadamantan- 2-carboxylic acid and via (R)-adamantylglycine. Molecular docking simulations of NOD2 receptor and prepared adamantly DMPs were also performed in order to investigate interactions established between DMPs and receptor protein.

desmuramyl peptides, NOD2 receptor, immunostimulation

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