Mechanism of DNA Binding and Cleavage

Abstract

The necessity for cellular regulation of DNA led to the development of metallonucleases to catalyze and repair DNA strand breaks. Due to cationic character, three-dimensional structural profiles, and propensity for performing hydrolysis, redox, or photoreactions of metal ions and complexes, have a natural ability for interacting with DNA. Since binding and cleavage of DNA is at the heart of cellular transcription and translation, it is an obvious target for therapeutic intervention and the development of diagnostic structural probes. Inorganic constructs such as cisplatin and its analogs exercise antitumor activity by inner-sphere coordination to DNA. During the last decades, the continuous evolution of artificial metallonucleases and metal-based chemotherapeutics such as cisplatin, photo-active octahedral metal complexes have been successfully used as DNA luminescent probes and light-driven reactive agents during the last decades. A recent emerging trend to improve their potential as molecular tools for studies of the genetic material is the design of bifunctional assemblies where the photo-active metal centre is tethered through a flexible linker to a nucleic acid recognition or reactive moiety. In this view, new metal complexes have been designed that utilize or create open coordination positions for DNA binding and hydrolysis, generate reactive oxygen containing species or other radicals for DNA oxidation, or perform direct redox reactions with DNA. This review briefly covers the aspects of drug molecule interaction factors, modes of DNA binding via groove binders, intercalators and alkylators along with the cleavage patterns such as hydrolytic, oxidative and photoinduced DNA cleavage, taking an example of Cisplatin and its mechanism.