Cellular Uptake of Aminoglycosides, Guanidinoglycosides, and Poly-arginine

Nathan W. Luedtke, Peter Carmichael, and Yitzhak Tor


Aminoglycosides (including neomycin B and tobramycin) exhibit poor uptake by eukaryotic cell lines. By converting the amines of these natural products into guanidine groups, their cellular uptake is dramatically enhanced. We have synthesized BODIPY-containing aminoglycosides and guanidinoglycosides to evaluate their cellular uptake properties. Fluorescence activated cells sorting (FACS) and fluorescence microscopy are used to compare the membrane translocation and the cellular localization of these compounds. Upon guanidinylation, the cellular uptake efficiencies of tobramycin and neomycin B are enhanced by 10-fold and 20-fold, respectively. Guanidino neomycin B exhibits a highly efficient uptake, superior to a fluorescent poly-arginine peptide. Interestingly, the cellular uptake of this common transduction peptide is inhibited by guanidino neomycin B, suggesting a similar uptake mechanism for both the arginine-rich peptides and the guanidinoglycosides.  

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