Designer aminoglycosides that selectively inhibit cytoplasmic rather than mitochondrial ribosomes show decreased ototoxicity a strategy for the treatment of genetic diseases

Abstract

Background: Whether the mitochondrial or cytoplasmic protein synthesis inhibition predominates to aminoglycosideinduced ototoxicity is unclear. Results: The ototoxicity of an aminoglycoside correlates primarily with its ability to block mitochondrial rather than cytoplasmic protein synthesis. Conclusion: Designer aminoglycosides that selectively inhibit cytoplasmic rather than mitochondrial ribosome show decreased ototoxicity. Significance: The results are beneficial for development of aminoglycoside-based drugs to treat human genetic diseases. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.