Interaction with plasmid DNA of Hoechst-TACN conjugates

Abstract

Interaction with plasmid DNA of Hoechst-TACN conjugatesA 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 curvature of the Hoechst skeletons thus forcing the TACN ligand to exit the minor groove and interact with the phosphate backbone of DNA. The conjugates and their Cu(II) and Zn(II) complexes interact strongly with DNA preserving the typical mode of binding of the Hoechst ligand.The strength of the interaction is strongly influenced by the nature of the linker, with the more hydrophobic being more efficient, and less by the presence and nature of the coordinated metal ion. In the case of the Zn(II) complex bearing a C6 linear alkyl linker a modest but reproducible acceleration of the hydrolytic cleavage of DNA has been observed which can be ascribed to the ability of the conjugate to deliver the hydrolytic subunit close to the DNA phosphate backbone.

Nuclease-like metalloscissors: Biomimetic candidates for cancer and bacterial and viral infections therapy

“…v) Construction of metallomicell catalysts from the self-assembly of amphiphilic metal complexes [89] , [90] , [91] . vi) Conjugation of metal complexes with bioactive molecules such as peptides, nucleotides, and vitamins as well as DNA binders to recognize specific targets and promote highly efficient catalytic reaction [92] , [93] , [94] , [95] , [96] , [97] , [98] , [99] . vii) Nanoformulation of metal complexes with nanoparticles (nano-nucleases) to obtain cooperative systems with enhanced nuclease-like activity [41] , [90] , [100] , [101] , [102] , [103] , [104] , [105] , [106] , [107] .…”