Chronic inflammatory disorders, such as Inflammatory Bowel Disease, arise from an inappropriate immune response to bacteria. It has long been known that muramyl dipeptide (MDP), a fragment of bacterial cell wall is able to generate an immune response.  Recently, it has been shown that the intracellular, mammalian protein Nod2 is involved in sensing the presence of MDP in the cell, leading to activation of the synthesis of inflammatory molecules.  Nod2 is an important protein to human health, as mutations in the gene have shown an increased incidence of Crohn's disease.  The mechanism of activation of the Nod2 signaling pathway by MDP is not understood. We have taken a chemical biological approach to this problem by synthesizing tagged versions of MDP. We describe the development of a variety of binding assays and present a model for Nod2 activation via MDP.  We present the first data for an MDP/Nod2 direct interaction.

Chemical tools for studying the activation of the intracellular innate immune protein Nod2

244th National Meeting (2012)

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