Synthesis of Neomycin-DNA/ Peptide Nucleic Acid Conjugates

Aminoglycoside antibiotics (Figs. 1 and 2), containing a unique polyamine/ carbohydrate structure, have attracted considerable attention because of their specific interactions with RNA. Their antibacterial activity is mainly exerted by their binding to the RNA of the bacterial ribosome, and thus interfering with the mRNA translation process. The miscoding causes membrane damage, which eventually disrupts cell integrity, leading to bacterial cell death. Aminoglycosides bind to various RNA molecules such as ribosomal RNA, 50-untranslated region of thymidylate synthase mRNA, both the Rev response element and the transactivating response element RNA motifs of HIV-1, and a variety of catalytic RNA molecules such as group I introns, ribonuclease P RNA, hairpin ribozyme, hammerhead ribozyme, and hepatitis delta virus ribozyme.