A new strategy for the preparation of distinct N-substituted muropeptides is described. Different orthogonally N-protected disaccharide thioglycosides were designed and synthesized. Among them, compound 4, qualified as a key intermediate, was utilized for further chemical transformations to develop a series of diverse N-substituted-glucosaminyl N-substituted-muramyl dipeptides (GMDPs). These unique muropeptides were applied for the study of human NOD2 stimulation. Intriguingly, structural modification of the MurNAc residue to N-non-substituted muramic acid (MurNH2 ) in GMDP dramatically impaired NOD2 stimulatory activity, but GMDPs possessing the glucosamine residue with a free amino group retained NOD2 stimulation activity. This work is the first study to illustrate the impact of both N-substituents of GMDPs on immunostimulatory activities of human NOD2.
Keywords: Bacterial peptidoglycan; Divergent synthesis; Innate immune; N-Substituted Disaccharide Dipeptides; NOD2.
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