Targeting an Artificial Metal Nuclease to DNA by a Simple Chemical Modification and Its Drastic Effect on Catalysis

Abstract

A novel metal complex was synthesized containing a purine derived ligand in order to increase its binding to DNA. We observed a huge increase in nuclease activity and, quite interestingly, an improvement on DNA sequence selectivity. A potential site of specific cleavage in the presence of a reductant in the reaction medium is suggested. We were able to synthesize a novel metal nuclease with improved activity on DNA, and with sequence specificity when exposed to a coreactant, this opens up new possibilities to create site specific and redox status modulated artificial nucleases.

A focus on the biological targets for coinage metal-NHCs as potential anticancer complexes

“…Some metal complexes can act as artificial nucleases able to cleave the phosphodiester bond of DNA causing its fragmentation and degradation [137][138][139]. Compound 97, one of the few copper(I) NHCs investigated for their anticancer potentialities, was cytotoxic in the submicromolar range against various cancer cell lines and could convert the supercoiled plasmid pcDNA4TO into its open circular form under aerobic conditions [140].…”

Anti-Proliferation and DNA Cleavage Activities of Copper(II) Complexes of N3O Tripodal Polyamine Ligands

“…Polypyridyl ligands have been widely used for designing copper nucleases because pyridines can intercalate into DNA and give rise to Cu II /Cu I redox potentials adequate for oxidative cleavage when engaged in coordination [16,17]. They are mostly based on bipyridine [18][19][20], phenanthroline [18,19,[21][22][23][24][25][26][27], terpyridine [28], phenanthrene [1,29], and tripodal structures [17,[30][31][32][33]. These moieties can be further engineered for adding functionalities [34,35].…”

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] .…”