Targeted chemical nucleases have a wide range of untapped applications in biological fields, including gene therapy

A feasible alternative to state-of-the-art enzymatic nucleases was created by regulating the cleavage activity of metal complexes using (covalent or non-covalent) homing agents. Targeted AMNs, unlike enzymatic nucleases, break DNA by an oxidative mechanism and can therefore permanently knock off genes. Compared to larger enzymatic nucleases, the modest size of the metal complex may aid cellular transfection. Furthermore, the painstaking construction of the sequence-specific probe permits a metal complex to be directed to dsDNA's minor or major groove. To direct the chemical reactivity of several small-molecule compounds to dsDNA's minor groove, covalently bonded polyamide samples were used. PNA and DNA were also used to construct antisense and antigen hybrids, with Watson–Crick or Hoogsteen base pairing with major groove nucleobases giving sequence recognition. Click chemistry created chimeric AMN-TFOs with desirable focused effects and negligible off-target cleavage. Clip-Phen-modified TFOs, 230 polypyridyl-modified TFOs, 232 and intercalating phenanthrene-modified TFOs are three contemporary instances of copper AMN–TFOs. All three systems have distinct advantages in maintaining the desired 2:1 phenthroline/copper ratio for DNA cleavage (clip-Phen TFOs), caging the copper center and facilitating efficient ROS-mediated strand scission (polypyridyl-modified TFO) and improving triplex stability (polypyridyl-modified TFO) (phenanthrene-TFOs). Cerium (IV)/EDTA complexes, recently shown to bind and hydrolytically cleave ssDNA/dsDNA junctions and used in conjunction with PNA to successfully introduce genome changes in vitro and in vivo, are another important class of targeted chemical nucleases. The chemical reactivity and wide flexibility of metal complex design, combined with their coupling to sequence specific samples for directed applications, show that these compounds have a wide range of untapped applications in biological fields such as chemotherapy, protein engineering, DNA footprinting, and gene editing. Parallel advancements in cell and tissue targeting will be essential to maximise their therapeutic potential, either by using specific ligands or creating new targeting modalities.

Synthesis, structural characterization and DNA studies of trivalent cobalt complexes of (2E)-4N-substituted-2-[4-(propan-2-yl)benzylidene]hydrazinecarbothioamide

This paper describes trivalent cobalt complexes of hydrazinecarbothioamides derived from 4-(propan-2-yl) benzaldehyde and substituted thiosemicarbazides NH2NHC(S)NHR, where R = H (1), Me (2), Et (3) or Ph (4) have been synthesized and characterized. The prepared ligands and complexes were characterized using various physicochemical techniques viz. elemental analysis, molar conductance, magnetic susceptibility measurements, IR, electronic absorption spectral studies and cyclic voltammetry. The electronic spectra in DMSO solvent and magnetic susceptibility data of complexes reveal that the complexes are diamagnetic with low spin octahedral cobalt(III) complexes. The absorption titration studies revealed that each of these complexes is an avid binder to calf thymus-DNA. The apparent binding constants are in the order of 107–108 M-1 . The nucleolytic cleavage activities of the ligands and their complexes were assayed on pUC18 plasmid DNA using gel electrophoresis in the presence and absence of H2O2. The ligands showed increased nuclease activity when administered as cobalt complexes. All the complexes behave as efficient chemical nucleases with hydrogen peroxide activation. These studies revealed that the complexes exhibit both oxidative and hydrolytic chemistry in DNA cleavage.

Protein engineering with artificial chemical nucleases

The process of protein engineering using artificial chemical nucleases is reported using the Cu(ii)-bis-1,10-phenanthroline complex.