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Published on: May 4, 2018
Peptidoglycan Modifications Tune the Stability and Function of the Innate Immune Receptor Nod2
James E Melnyk1, Vishnu Mohanan1, Amy K Schaefer1
1†Department of Chemistry and Biochemistry, and §Department of Biological Sciences, University of Delaware, Newark, Delaware 19716, United States.
Abstract:
Natural modifications of peptidoglycan modulate the innate immune response. Peptidoglycan derivatives activate this response via the intracellular innate immune receptor, Nod2. To probe how these modifications alter the response, a novel and efficient carbohydrate synthesis was developed to allow for late-stage modification of the amine at the 2-position. Modification of the carbohydrate was found to be important for stabilizing Nod2 and generating the proper response. The native Nod2 ligands demonstrate a significant increase in the cellular stability of Nod2. Moreover, changing the identity of the natural ligands at the carbohydrate 2-position allows for the Nod2-dependent immune response to be either up-regulated or down-regulated. The ligand structure can be adjusted to tune the Nod2 response, suggesting that other innate immune receptors and their ligands could use a similar strategy.
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