Journal of the American Chemical Society
Communication
very high concentrations (200 μM) of 1 led to the degradation of
Nod222 when protein synthesis is not inhibited, suggesting there
are other feedback mechanisms to control Nod2 levels in the cell.
The data presented here demonstrate the ability to modulate
Nod2 stability via natural or unnatural variation at the site of
acetylation.
In their natural environments, virulent bacteria modify their
peptidoglycan to evade detection by the innate immune
system.3,23 Acetylation of the 6-position of the carbohydrate
and deacetylation of the 2-postion prevents cell wall degradation
by lysozyme.3c,d Interestingly, these data demonstrate that
deacetylation of the 2-postion also eliminates the ability of the
peptidoglycan fragment to signal through the Nod2-dependent
pathway. Acetylation of the 6-position does not affect the ability
to stimulate the Nod2-dependent immune response.11a These
data suggests that the deacetylation strategy used by bacteria is
two-pronged in that the modification (3) yields lysozyme-
resistant peptidoglycan that does not elicit an immune response
via the Nod2-dependent pathway.
is a Pew Scholar in the Biomedical Sciences, supported by the
Pew Charitable Trusts. We thank Neal Zondlo, John Koh, and
Thomas Hanson for critical reading of this manuscript.
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ASSOCIATED CONTENT
* Supporting Information
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Experimental procedures, spectral data, NF-κB assay conditions,
detailed half-life protocols, Western blot analysis, and complete
refs 3c, 5a, 6, and 12b. The Supporting Information is available
AUTHOR INFORMATION
Corresponding Author
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Notes
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The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
This publication was made possible by the Delaware COBRE
program, supported by a grant from the National Institute of
General Medical Sciences (NIGMS 1 P30 GM110758 and 1 P20
GM104316-01A1) from the National Institutes of Health. C.L.G.
D
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX