This proposal addresses the development of an aminoglycoside mimetic library that can be used to target specific sequences of RNA. Specifically, these mimetics will be targeted at a synthetic 5'- biotinylated-stem-loop RNA which contains the conserved A-site of prokaryotic 16S ribosomal RNA (rRNA) to which aminoglycosides are known bind. The library will be assayed for RNA-binding activity using a streptavadin-linked probe. Compounds that bind the A-site of prokaryotic rRNA are expected to posses strong antibiotic activity. in its larger context, the proposal aims to show how aminogycosides, by conjugation with amino acids, could be used as monomers in a combinatorial syntheses to build a new class of antisense or antigene agents.
