Ligands for Abasic Site-containing DNA and their Use as Fluorescent Probes

Abstract

Apurinic and apyrimidinic sites, also referred to as abasic or AP sites, are residues of duplex DNA in which one DNA base is removed from a Watson-Crick base pair. They are formed during the enzymatic repair of DNA and offer binding sites for a variety of guest molecules. Specifically, the AP site may bind an appropriate ligand as a substitute for the missing nucleic base, thus stabilizing the abasic site-containing DNA (AP-DNA). Notably, ligands that bind selectively to abasic sites may be employed for analytical and therapeutical purposes. As a result, there is a search for structural features that establish a strong and selective association of a given ligand with the abasic position in DNA. Against this background, this review provides an overview of the different classes of ligands for abasic site-containing DNA (AP-DNA). This review covers covalently binding substrates, namely amine and oxyamine derivatives, as well as ligands that bind to AP-DNA by noncovalent association, as represented by small heterocyclic aromatic compounds, metal-organic complexes, macrocyclic cyclophanes, and intercalator-nucleobase conjugates. As the systematic development of fluorescent probes for AP-DNA has been somewhat neglected so far, this review article contains a survey of the available reports on the fluorimetric response of the ligand upon binding to the AP-DNA. Based on these data, this compilation shall present a perspective for future developments of fluorescent probes for AP-DNA.

Keywords: DNA recognition; Nucleic acids; cancer; fluorescence; heterocyclic arenes; metal-organic compounds.