Interaction with plasmid DNA of Hoechst-TACN conjugates

ABSTRACT

A new family of conjugates between the Hoechst minor groove binder and the TACN metal ion ligand connected through hydrophobic alkyl or more hydrophilic oxyethyl linkers of different length has been prepared. The linkers are connected to the convex side of the Hoechst skeleton thus forcing the TACN ligand to exit the minor groove and interact with the phosphate backbone of DNA. The conjugates preserve the binding mode of Hoechst with an affinity influenced by the nature of the linker, the more hydrophobic being the more efficient. Coordination of Cu(II) or Zn(II) poorly affect these parameters. Nevertheless, the Zn(II) complex bearing a C6 linear alkyl linker induced a modest but reproducible acceleration of the hydrolytic cleavage of DNA which can be ascribed to the ability of the conjugate to deliver the hydrolytic subunit close to the DNA phosphodiester bonds.

GRAPHICAL ABSTRACT

KEYWORDS:

• Synthetic nucleases
• Hoechst
• TACN
• Zn(II) and Cu(II) complexes
• DNA cleavage

Acknowledgments

The authors thank dr. Ilaria Furlan for her involvement in a part of the synthetic work. This work was supported by the MSCA-ITN MMBIO (721613) project.

Disclosure statement

No potential conflict of interest was reported by the authors.