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tions. Muraymycin D1-diamide (3) shows significantly
greater inhibition of the WecA enzyme than its natural
form. To date, only a few investigational TB drugs such as
UT-01320 and CPZEN-45 have been reported to inhibit
2
2
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25,26
the WecA enzymes at low concentrations.
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the activity of muraymycin A1 has been evaluated in vitro
1
a
and in vivo, the antibacterial activity of the other mu-
raymycins (B, C and D) has not been thoroughly investi-
gated. Interestingly, we have identified that muraymycin
D1 shows strong bacteriostatic activity against M. tubercu-
losis by targeting both MurX and WecA enzymes. Amide
derivatives of muraymycins can be purified readily via
conventional methods without the need for HPLC purifi-
cation. These chemical properties will facilitate the dis-
covery of new muraymycin analogs. Application of the
synthetic strategies presented here continues for the syn-
thesis of muraymycin A1 and its analogs in our laboratory.
Efficacy of muraymycin congeners against non-replicating
M. tuberculosis will be reported elsewhere.
0
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Supporting Information
The Supporting Information is available free of charge on the
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Complete experimental details, compound characteriza-
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The authors declare no competing financial interests.
(
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(
ACKNOWLEDGMENTS
2
The National Institutes of Health is greatly acknowledged
for financial support of this work (AI084411 and
GM114611). MK thanks University of Tennessee for gener-
ous financial support (CORNET Award). NMR data were
obtained on instruments supported by the NIH Shared
Instrumentation Grant. The following reagent was ob-
tained through BEI Resources, NIAID, NIH: M. tuberculo-
sis, Strain H37Rv and Gamma-Irradiated M. tuberculosis,
NR-14819. We gratefully acknowledge Dr. William
Clemons (California Institute of Technology) for useful
discussions of the WecA assays.
(
1
(
(
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REFERENCES AND NOTES
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