Library construction of neomycin–dipeptide heteroconjugates and selection against RRE RNA Original Research Article

An approach is described to the design of neomycin–dipeptide conjugates as ligands for Rev responsive element (RRE) RNA, which effectively inhibit Rev–RRE interaction. A library of 256 neomycin–dipeptide conjugates was constructed on TentaGel beads using a split-and-pool combinatorial synthesis. Five conjugates were selected after screening the library with fluorescence linked RRE RNA, and they were identified after sequencing by MALDI-TOF mass spectrometer. The heteroconjugates bind to RRE RNA with moderately improved affinities and highly improved specificity, compared to neomycin as determined by means of fluorescence anisotropy and surface plasmon resonance (SPR) experiments. This strategy, synthesis of the neomycin–peptide heteroconjugate library and selection against RNA target, could provide an efficient way to develop inhibitors against pathogenic RNA.