Antofine analogues can inhibit tobacco mosaic virus assembly through small-molecule-RNA interactions

The extra unpaired base(s) or bulged structures of nucleic acids are capable either of forming complexes with nucleic-acid-binding proteins or of acting as binding sites for small molecules. We are interested in developing bulge-specific agents as potential drugs or chemical tools in biological research. Antofine can selectively bind with DNA and RNA bulged structures (Xi et al., Bioorg. Med. Chem. Lett. 2006, 16, 4300-4304). Furthermore, a series of antofine analogues suitable for selective binding with TMV RNA rather than with TMV coat protein (CP) were found. Biochemical studies indicated that antofine and its analogues disrupt in vitro virus assembly through small-molecule-RNA interactions. A structural model to illustrate these effects has been proposed. It is suggested that antofine analogues bind selectively with RNA bulged structures and therefore disrupt interaction between TMV RNA and TMV CP.