Targeting RNA with Aminoglycosides: Current Improvements in their Synthesis and Biological Activity
Pp. 131-209 (79)
Andrés G. Santana, Sandra G. Zárate, Agatha Bastida and Julia Revuelta
RNA has been considered during a long time as an intermediate between two biomolecules
of special relevance in the life: the DNA (an nucleic acid that encodes the genetic
instructions in all known living organisms) and proteins (molecules that perform a vast array
of functions within living organisms). However, recent discoveries have converted this
molecule in the spotlight of biomedical research. To this must be added that scientific
community has explored only the tip of the iceberg of potential of RNA-binding drugs as
therapeutic agents, except the antibiotics which exert their action by binding to rRNA. In this
context, aminoglycoside compounds are a family of natural pseudo-oligosaccharides
positively charged, which have been used for a long time as antibiotics that bind ribosomal
RNA and whose use has been relegated today for two reasons: their inherent toxicity and the
development for bacterial of several resistance mechanisms to those. Nevertheless, these
drawbacks are in the way to be solved because several aminoglycosides with lower toxicity
and potential to overcome resistance have been discovered in the last decade. Besides, in this
period it has been described the possibility of using these compounds as ligands of other
RNA targets, such as HIV-RNA.
In this chapter, current applications of natural and semi-synthetic aminoglycosides both
as antibacterials and as antivirals/HIV as well as their corresponding mechanisms will
Aminoglycosides, antibiotics, antivirals, bacteria, drugs, HIV,
oligosaccharides, resistance, RNA, synthesis, toxicity.
Institute of General Organic Chemistry of the Spanish National Research Council, Department of Bioorganic Chemistry, Madrid, Spain.