3wru

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=SJP:(2R,3R)-4-AMINO-N-[(1R,2S,3R,4R,5S)-5-AMINO-4-[(2,6-DIAMINO-2,3,4,6-TETRADEOXY-ALPHA-D-ERYTHRO-HEXOPYRANOSYL)OXY]-3-{[3-O-(2,6-DIAMINO-2,3,4,6-TETRADEOXY-BETA-L-THREO-HEXOPYRANOSYL)-BETA-D-RIBOFURANOSYL]OXY}-2-HYDROXYCYCLOHEXYL]-3-FLUORO-2-HYDROXYBUTANAMIDE'>SJP</scene></td></tr>

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== Publication Abstract from PubMed ==

Aminoglycoside antibiotics are pseudosaccharides decorated with ammonium groups that are critical for their potent broad-spectrum antibacterial activity. Despite over three decades of speculation whether or not modulation of pKa is a viable strategy to curtail aminoglycoside kidney toxicity, there is a lack of methods to systematically probe amine-RNA interactions and resultant cytotoxicity trends. This study reports the first series of potent aminoglycoside antibiotics harboring fluorinated N1-hydroxyaminobutyryl acyl (HABA) appendages for which fluorine-RNA contacts are revealed through an X-ray cocrystal structure within the RNA A-site. Cytotoxicity in kidney-derived cells was significantly reduced for the derivative featuring our novel beta,beta-difluoro-HABA group, which masks one net charge by lowering the pKa without compromising antibacterial potency. This novel side-chain assists in evasion of aminoglycoside-modifying enzymes, and it can be easily transferred to impart these properties onto any number of novel analogs.

Toxicity modulation, resistance enzyme evasion, and A-site X-ray structure of broad-spectrum antibacterial neomycin analogs.,Maianti JP, Kanazawa H, Dozzo P, Matias RD, Feeney LA, Armstrong ES, Hildebrandt DJ, Kane TR, Gliedt MJ, Goldblum AA, Linsell MS, Aggen JB, Kondo J, Hanessian S ACS Chem Biol. 2014 Sep 19;9(9):2067-73. doi: 10.1021/cb5003416. Epub 2014 Jul, 14. PMID:25019242<ref>PMID:25019242</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 3wru" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Armstrong, E S]]

[[Category: Dozzo, P]]

[[Category: Feeney, L A]]

[[Category: Hanessian, S]]

[[Category: Kanazawa, H]]

[[Category: Kondo, J]]

[[Category: Maianti, J P]]

[[Category: Rna-antibiotic complex]]