(P)-Helicene Displays Chiral Selection in Binding to Z-DNA

摘要

Left-handed Z-form DNA is one of the significant characteristic DNA local structures. It has been extensively investigated in relation to transcription, the methylation of cytosine, and the level of DNA supercoiling.1 Rich and colleagues discovered that double-stranded RNA adenosine deaminase (ADAR1) and the tumor-associated protein, DLM-1, specifically bind to Z-DNA. Recently, the biological relevance of Z-DNA has been further demonstrated by Lui and colleagues. They provided the first evidence that Z-DNA-forming sequences are required for chromatin-dependent activation of the CSF1 promoter. Recently, there has been increased attention focused on the binding of small molecules to specific DNA structures to inhibit the biological functions in which these particular structures participate. Norden and Tjerneld first reported that the A enantiomer of tris-(dipyridyl)Fe(Ⅱ) binds to right-handed B-form DNA. The Barton laboratory developed a series of chiral metal molecules that recognize specific DNA structures including Z-DNA, but the molecular basis of enantioselectivity is not well understood. Although the anticancer agent (+)-daunorubicin and its novel (-)-enantiomer (WP900) display enantioselectivity in binding to DNA, as reported by Qu and colleagues, the synthesis of WP900 is no easy undertaking, requiring some 37 steps. We report here a simple helicene molecule that displays structural selectivity in binding to DNA (Figure 1). We found that the (P)-A and (M)-A enantiomeric pair can discriminate between B- and Z-DNA and that (P)-A selectively binds Z-DNA and effectively converts the B-DNA conformation to Z-DNA.