Guanidinoglycosides: A Novel Family of RNA Ligands

Nathan W. Luedtke, Tracy J. Baker, Murray Goodman, and Yitzhak Tor

Abstract

We have designed and synthesized a new family of RNA ligands termed "guanidinoglycosides", by converting all of the ammonium groups present in aminoglycosides into guanidinium groups.  Fluorescence anisotropy and a new solid-phase assay are used to determine the relative affinity and specificity of each guanidinoglycoside for the HIV-1 RRE (Rev Response Element).  Upon guanidinylation, a substantial increase in RRE affinity is seen for all glycosides tested.  The RNA specificity is also affected; guanidinylation of tobramycin increases its selectivity for the RRE, while guanidinylation of neomycin decreases its RRE selectivity.  Similar to aminoglycosides, all guanidinoglycosides bind RNA preferentially over DNA.  Guanidinoglycosides are new tools for the study of RNA–small molecule interactions, and have potential applications as new antiviral agents.

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