CARB 54 |
| The conjugation of aminoglycosides with small molecules has been shown to enhance affinity and specificity for RNA targets. In this study, a novel drug has been designed by the conjugation of the aminoglycoside neomycin B with the antibiotic doxycycline, using a poly(ethylene glycol) (PEG) linker. This conjugate is designed to target rRNA at the A-site of the prokaryotic ribosome. Molecular modeling was used to determine that PEG-400 will provide the best fit for the target site, and computational docking studies suggest that the affinity of the conjugate will be stronger than that of either drug alone. The binding conformation of each drug from crystal structure was used to design the necessary synthetic modifications. A ten-step synthesis was employed, including several modifications to neomycin, attachment to PEG via amide coupling, and addition to doxycycline by aromatic substitution. Spectroscopic methods were then used to characterize the novel conjugates. |
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General Posters
6:00 PM-8:00 PM, Tuesday, March 27, 2007 Hyatt Regency Chicago -- Riverside Center, Poster
Division of Carbohydrate Chemistry |