Sequence-specific recognition of right-handed double-helical DNA by (2S,3S)- and (2R,3R)-dihydroxybis(netropsin)succinamide

Abstract

We report a class of chiral sequence-specific DNA binding molecules based on two netropsin analogues and the enantiomers of dl-tartaric acid: (2R,3R)- and (2S,3S)-dihydroxybis(netropsin)succinamide-EDTA [(R,R)- and (S,S)-1, respectively] (Figures 1 and 2). The enantiomeric threo-(R,R)1 and -(SS)-1 should afford diastereomeric complexes at common binding sites on double-helical DNA (Figure 1). Attachment of EDTA to one terminus of the crescent-shaped hexamides allows use of the affinity cleaving method to determine the differences between (R,R)-1•Fe^(II) and (S,S)-1•Fe^(II) with regard to relative binding affinities, sequence specificities, and orientations by analysis of the DNA-cleavage patterns on a 32P end-labeled DNA restriction fragment using high-resolution gel electrophoresis. For comparison to the enantiomers of 1, bis(netropsin)succinamide-EDTA (2) was synthesized (Figure 2).