Biological studies of muramyl dipeptide analogues as potential ligands for NOD2 receptor

Abstract

The human body’s survival against various foreign disease-causing organisms solely depends on the protection provided by our body's immune system. Our body's complex yet effective immune system comprises cells, molecules and sensory receptors that can activate various immune response pathways to eliminate pathogens. The innate immune system provides the first line of defence through different types of sensor cells with pattern recognition receptors (PRRs) with cytoplasmic proteins like NOD-like receptors (NLRs) that can activate the innate immune system by recognizing the bacterial cell wall component peptidoglycan. The smallest known fragment of peptidoglycan is Muramyl Dipeptide (MDP) which is recognized by the Nucleotide-binding oligomerization domain (NOD2) receptor of the NLR family as a pathogenassociated molecular pattern and can immediately activate the human body's innate immune system to release effective mediators that dominate the destruction of invading pathogens and with adverse side-effects. The parent MDP molecule exhibits high toxicity, hydrophilicity, and rapid elimination from the biological system. Modifications to the MDP structure without losing their immunomodulatory properties can be evaluated to separate desirable biological activities from unwanted side effects that can enhance and modulate the innate immune response and can further be evaluated for their adjuvant potency in vaccines and drugs. [...]