Antibacterial Aminoglycosides with a Modified Mode of Binding to the Ribosomal-RNA Decoding Site

A new twist of RNA fate: Site‐selective chemical functionalization at the C2′′OH group of paromomycin (1) afforded a novel analogue with potent inhibitory activity against several bacterial strains, including a multidrug‐resistant S. aureus (MRSA) strain. X‐ray cocrystal‐structure determination of...

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Veröffentlicht in:	Angewandte Chemie International Edition 2004-12, Vol.43 (48), p.6735-6738
Hauptverfasser:	François, Boris, Szychowski, Janek, Adhikari, Susanta Sekhar, Pachamuthu, Kandasamy, Swayze, Eric E., Griffey, Richard H., Migawa, Michael T., Westhof, Eric, Hanessian, Stephen
Format:	Artikel
Sprache:	eng
Schlagworte:	aminoglycosides Anti-Bacterial Agents Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - metabolism Anti-Bacterial Agents - pharmacology antibacterial agents bacterial resistance Biochemistry, Molecular Biology drug design Life Sciences Models, Molecular Molecular Conformation Molecular Structure Paromomycin Paromomycin - chemistry Paromomycin - metabolism Paromomycin - pharmacology Research Support, Non-U.S. Gov't RNA, Ribosomal RNA, Ribosomal - genetics RNA, Ribosomal - metabolism rRNA Structure-Activity Relationship
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Zusammenfassung:	A new twist of RNA fate: Site‐selective chemical functionalization at the C2′′OH group of paromomycin (1) afforded a novel analogue with potent inhibitory activity against several bacterial strains, including a multidrug‐resistant S. aureus (MRSA) strain. X‐ray cocrystal‐structure determination of the complex with the A site of E. coli RNA revealed a new mode of binding in which significant conformational and positional changes had taken place in rings III and IV.
ISSN:	1433-7851 1521-3773
DOI:	10.1002/anie.200462092