ACS Medicinal Chemistry Letters
Letter
(16) Uehara, Y.; Hori, M.; Kondo, S.; Hamada, M.; Umezawa, H.
Structure-activity relationships among negamycin analogs. J. Antibiot.
ACKNOWLEDGMENTS
■
Many analogues were synthesized in collaboration with
Pharmaron Corporation. We thank Sara Patey, Linda Otterson,
Marie Potter, and Robert Giaccobe for carrying out MIC
measurements, Jian Huang for TT assays, and Mark
Zambrowski, Sharon Tantarelli, Nancy DeGrace, and Camil
Joubran for analytical chemistry support.
(17) Buurman, E. T.; Foulk, M. A.; Gao, N.; Laganas, V. A.;
McKinney, D. C.; Moustakas, D. T.; Rose, J. A.; Shapiro, A. B.;
Fleming, P. R. Novel rapidly diversifiable antimicrobial RNA
polymerase switch region inhibitors with confirmed mode of action
in Haemophilus influenzae. J. Bacteriol. 2012, 194 (20), 5504−12.
(18) Raju, B.; Anandan, S.; Gu, S.; Herradura, P.; O’Dowd, H.; Kim,
B.; Gomez, M.; Hackbarth, C.; Wu, C.; Wang, W.; Yuan, Z.; White, R.;
Trias, J.; Patel, D. V. Conformationally restricted analogs of
deoxynegamycin. Bioorg. Med. Chem. Lett. 2004, 14 (12), 3103−7.
(19) Raju, B.; Mortell, K.; Anandan, S.; O’Dowd, H.; Gao, H.;
Gomez, M.; Hackbarth, C.; Wu, C.; Wang, W.; Yuan, Z.; White, R.;
Trias, J.; Patel, D. V. N- and C-terminal modifications of negamycin.
Bioorg. Med. Chem. Lett. 2003, 13 (14), 2413.
(20) Polikanov, Y. S.; Szal, T.; Jiang, F.; Gupta, P.; Matsuda, R.;
Shiozuka, M.; Steitz, T. A.; Vazquez-Laslop, N.; Mankin, A. S.
Negamycin interferes with decoding and translocation by simultaneous
interaction with rRNA and tRNA. Mol. Cell 2014, 56 (4), 541−50.
(21) Olivier, N. B.; Altman, R. B.; Noeske, J.; Basarab, G. S.; Code,
E.; Ferguson, A. D.; Gao, N.; Huang, J.; Juette, M. F.; Livchak, S.;
Miller, M. D.; Prince, D. B.; Cate, J. H.; Buurman, E. T.; Blanchard, S.
C. Negamycin induces translational stalling and miscoding by binding
to the small subunit head domain of the Escherichia coli ribosome. Proc.
Natl. Acad. Sci. U. S. A. 2014, 111 (46), 16274−9.
ABBREVIATIONS
■
DEAD, diethylazodicarboxylate; DMF, dimethylformamide;
GPCR, G-coupled protein receptor; MHA, methylhydrazine-
acetic acid; MIC, minimum inhibitory concentration; SAR,
structure−activity relationship; smFRET, single molecule
fluorescence resonance energy transfer; THF, tetrahydrofuran;
TT, coupled transcription-translation
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