Synthesis and validation of click-modified of NOD1/2 agonists [preprint]
Anonick, Madison V.
Wodzanowski, Kimberly A.
Grimes, Catherine L.
UMass Chan AffiliationsMedicine
Program in Innate Immunity
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AbstractNOD1 and NOD2 sense small bacterial peptidoglycan fragments often called muropeptides. These muropeptides include iE-DAP and MDP, the minimal agonists for NOD1 and NOD2, respectively. Here, we synthesized and validated alkyne-modified muropeptides, iE-DAP-Alk and MDP-Alk, for use in click-chemistry reactions. While it has long been known that many cell types respond to extracellular exposure to muropeptides, it is unclear how these innate immune activators access their cytosolic innate immune receptors, NOD1 and NOD2. The subcellular trafficking and transport mechanisms by which muropeptides access these cytosolic innate immune receptors are a major gap in our understanding of these critical host responses. The clickchemistry-enabled agonists developed here will be particularly powerful to decipher the underlying cell biology and biochemistry of NOD1 and NOD2 innate immune sensing.
SourceSynthesis and validation of click-modified of NOD1/2 agonists. Ravi Bharadwaj, Madison V. Anonick, Siavash Mashayekh, Ashley Brown, Kimberly A. Wodzanowski, Kendi Okuda, Neal Silverman, Catherine L. Grimes. bioRxiv 2023.03.28.534546; doi: https://doi.org/10.1101/2023.03.28.534546
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/51913
NotesThis article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.
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Except where otherwise noted, this item's license is described as The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.