Our bodies house trillions of beneficial bacteria, and misrecognition of these bacteria as pathogenic is thought to cause a variety of autoimmune disorders such as inflammatory bowel diseases (IBDs). Nucleotide oligomerization domain containing protein 2 (Nod2) is an innate immune receptor genetically linked to an IBD called Chron’s disease. Nod2 recognizes a fragment of the peptidoglycan known as Muramyl Dipeptide (MDP). Peptidoglycan is made up of repeating units of N-Acetylglucosamine and N-Acetylmuramic acid with alternating D,L amino acids (Figure 1). The amino acid sidechain is further cross-linked in bacteria to make a protective mesh like polymer. In this work, we have developed a synthetic route for MDP dimers, which mimic the amino acid cross-linking found in the bacteria’s cell wall. These synthetic dimers contain an alkyl chain linkage of varying lengths (Figure 1). These compounds will be screened for their ability to initiate a Nod2 dependent immune response <i>in vivo</i>, as well as their ability to stabilize Nod2. Addition of a free amine linker to these compounds allows functionalization to Surface Plasmon Resonance (SPR) as well as to our carbohydrate microarray to determine binding not only with Nod2 but also other innate immune receptors expressed in our lab.

Total synthesis of muramyl dipeptide dimers

256th National Meeting (2018)

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