A method for designing compounds specifically targeting RNA sequences,
based on the discovery of short, specific sequences within RNA that are
critical to function, using modeling of the compound to effect binding to
the nucleotide sequences in the RNA in combination with secondary and/or
tertiary structure associated with the minor groove of the RNA in the
region of the critical sequences. In the preferred method, computer
modeling is used along with analysis of the targeted RNA sequence to
design molecules binding to the targeted RNA by covalent or hydrogen
binding. Appropriate molecules are synthesized using known methodology
that have the required structure and chemical characteristics to
specifically bind the critical region of the RNA and thereby inhibit the
function of the RNA. Molecules known to bind to RNA can also be modified
using this method to increase specificity, and thereby decrease toxicity.