A bulge binding agent with novel wedge-shape topology for stimulation of DNA triplet repeat strand slippage synthesis

Expansion of DNA repeat sequences is associated with many human genetic diseases. Bulged DNA structures have been implicated as intermediates in DNA slippage within the DNA repeat regions. Herein a bulge binding agent with novel wedge-shape topology of the aromatic moiety was designed and synthesized. The compound–bulge DNA interactions were characterized via UV melting experiments, circular dichroism and were quantitated by surface plasmon resonance with Kd of 41.5 μM. This compound showed remarkable stimulation for DNA triplet repeat strand slippage synthesis in vitro.

A novel wedge-shaped bulge binder phenothiazine aminosugar was designed and synthesized, which could stimulate DNA slippage synthesis in vitro. The compound–DNA interactions were quantitated by surface plasmon resonance.Figure optionsDownload as PowerPoint slide