NOD2 is an intracellular pathogen receptor that plays a critical role in the maintenance of intestinal homeostasis and response to Gram positive and negative bacteria. Mutations in NOD2 have been implicated in several immune disorders such as Blau syndrome, sarciodosis and Crohn’s disease. Thus, it is increasingly important to develop appropriate tools for studying this critical pathway.  Solution phase syntheses have been applied extensively to obtain several analogues of MDP for probing the interactions with NOD2. Disadvantages of solution phase   functionalization are that solution phase requires extensive synthetic steps and also involves several purification steps of the intermediates. These laborious steps can be eliminated with solid-phase synthesis. The existing solid-phase approach does not address modifications of the Muramyl building block at the C-6 position. We have demonstrated that, chemical modifications of the muramyl moiety can be achieved on solid support  with orthogonally protected muramyl building block, which allows access to the C-6 position of MDP for tethering various probes to enhance and expand on the available tools for studying interactions of MDP and NOD2.  Thus a facile synthetic approach for obtaining several analogues of MDP on solid phase has been described.

Design and solid-phase synthesis of Muramyl dipeptide (MDP) surrogates as NOD2 signaling activating agents

253rd National Meeting (2017)

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