Designed sequence-specific minor groove ligands

In the past decade, a general design for sequence-specific minor groove lig ands has evolved, based on the natural products distamycin and netropsin. B y utilizing a basic set of design rules for connecting pyrrole, imidazole, and hydroxypyrrole modules, new ligands can be prepared to target almost an y sequence of interest with both high affinity and specificity. In this rev iew we present the design rules with a brief history of how they evolved. T he structural basis for sequence-specific recognition is explained, togethe r with developments that allow linking of recognition modules that enable t argeting of long DNA sequences. Examples of the affinity and specificity th at can be achieved with a number of variations on the basic design are give n. Recently these molecules have been used to compete with proteins both in vitro and in vivo, and a brief description of the experimental results are given.