A closer look at ligand specificity for cellular activation of NOD2 with synthetic muramyl dipeptide analogues

To further understand the specificity of muramyl dipeptide (MDP) sensing by NOD2, we evaluated the compatibility of synthetic MDP analogues for cellular uptake and NAGK phosphorylation, the pre-requisite steps of intracellular NOD2 activation. Our results revealed that these two prior steps do not c...

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Bibliographic Details
Main Authors: Adamson, Christopher, Liang, Yaquan, Feng, Shiliu, Ng, Allan Wee Ren, Qiao, Yuan
Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
Format: Article
Language:English
Published: 2024
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Online Access:https://hdl.handle.net/10356/174232
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Institution: Nanyang Technological University
Language: English
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Summary:To further understand the specificity of muramyl dipeptide (MDP) sensing by NOD2, we evaluated the compatibility of synthetic MDP analogues for cellular uptake and NAGK phosphorylation, the pre-requisite steps of intracellular NOD2 activation. Our results revealed that these two prior steps do not confer ligand stereoselectivity; yet NAGK strictly discriminates against the disaccharide NOD2 agonists for phosphorylation in vitro, despite it being indispensable for the cellular NOD2-stimulating effects of these analogues, implying potential glycosidase cleavage as a novel intermediate step for cellular activation of NOD2.