Convenient synthesis of NCS-chromophore metabolite isosteres: binding agents for bulged DNA microenvironments.

A designed molecule with capacity to bind DNA bulges (20) has been prepared from readily available starting materials. The spirocyclic template was modeled on a metabolite of neocarzinostatin chromophore (NCSi-gb) and is equipped with functionality to enable convenient bioassay. Preliminary studies confirm binding at specific bulged sequences and induction of polymerase-mediated slippage events. The target compound offers a convenient means to study affinity for unique bulged motifs and for use as a molecular biology reagent.