Synthesis, DNA binding and cleavage studies of the copper(II) complexes of PNA-cyclen conjugates

Abstract

Two dinucleotide PNA-cyclen copper(II) complexes with -PNA (P1) and classical PNA (P2) backbones were synthesized and characterized. The interactions between title complexes and DNA were investigated under physiological conditions. Fluorescence studies indicate that the binding ability of complex P1 to CT-DNA is as twice as that of P2. DNA melting experiments were also carried out and the results show that T m caused by P1 is higher than that caused by P2. Agarose gel electrophoresis experiments demonstrate that P1 is an excellent chemical nuclease, which can cleavage plasmid DNA completely in 12 h.

Toward Catalytic Antibiotics: Redesign of Fluoroquinolones to Catalytically Fragment Chromosomal DNA

“…Indeed, other studies have reported on similar copper complexes (bearing DNA intercalators) that cleave DNA via an oxidative pathway in the absence of adjuvants. 41,42 However, since the inhibitory effects of NaN 3 and KI could also be mediated by their ability to displace the copper-coordinated water, these data do not rule out the possibility that a hydrolytic mechanism contributes to the nuclease activity. Indeed, UV−vis spectroscopic analysis of the mixture of Cu(II)-cyclen with NaN 3 , KI, or NaCl (Supplementary Figures S4−6) reveal that NaN 3 and KI displace the Cu(II) associated water while the NaCl does not (i.e., at the ratio used in the scavenging assay).…”

Experimental and computational investigation of heteroatom substitution in nucleolytic Cu(ii) cyclen complexes for balancing stability and redox activity

“…In cell studies various nucleolytic copper complexes have shown high activity against cancer cells. [9][10][11] There are several approaches to increase the cleavage activity of cyclen metal complexes towards nucleic acids: multinuclear complexes, [12][13][14] attachment of nucleobase-affine moieties 15 or positively charged groups for better interaction with the phosphate backbone. 16 Whereas the 4N donor ligand cyclen has been frequently applied in such studies, heteroatom-substituted analogs are less common.…”

“…There are several approaches to increase the cleavage activity of cyclen metal complexes towards nucleic acids: multinuclear complexes, 12–14 attachment of nucleobase-affine moieties 15 or positively charged groups for better interaction with the phosphate backbone. 16…”