Poster abstracts
Poster number 144 submitted by Hongkun Zhu
Tobramycin Variants with Enhanced Ribosome-Targeting Activity
Marina Y. Fosso1 (Department of Pharmaceutical Sciences College of Pharmacy, University of Kentucky), Hongkun Zhu1 (Department of Microbiology Center for RNA Biology, Ohio State University), Keith D. Green (Department of Pharmaceutical Sciences College of Pharmacy, University of Kentucky), Sylvie Garneau-Tsodikova (Department of Pharmaceutical Sciences College of Pharmacy, University of Kentucky), Kurt Fredrick (Department of Microbiology Center for RNA Biology, Ohio State University)
Abstract:
With the increased evolution of aminoglycoside (AG)-resistant bacterial strains, the need to develop AGs with 1) enhanced antimicrobial activity, 2) the ability to evade resistance mechanisms, and 3) the capability of targeting the ribosome with higher efficiency is more and more pressing. The chemical derivatization of the naturally occurring tobramycin (TOB) by attachment of 37 different thioether groups at the 6''-position led to the identification of generally poorer substrates of TOB-targeting AG-modifying enzymes (AMEs). Thirteen of these displayed better antibacterial activity than the parent TOB while retaining ribosome-targeting specificity. Analysis of these compounds in vitro shed light on the mechanism by which they act and revealed three with clearly enhanced ribosome-targeting activity.
References:
Fosso MY, Zhu H, Green KD, Garneau-Tsodikova S, Fredrick K. ChemBioChem 2015, 16, 1565 – 1570.
Keywords: Aminoglycosides, Ribosome, Translocation