Comparison of phenanthriplatin, a novel monofunctional platinum based anticancer drug candidate, with cisplatin, a classic bifunctional anticancer drug

Abstract

Nucleotide excision repair, a DNA repair mechanism, is the major repair pathway responsible for removal of platinum-based anticancer drugs. In this study, 146 bp duplexes were prepared containing either a site-specific cisdiammineplatinum( Il)-DNA intrastrand d(GpG) cross-link or a cisdiamminephenanthridinechloroplatinum( Il)-DNA dG adduct. Comparison of the repair efficiencies of the two adducts reveals that the diamminephenanthridinechloroplatinum(lI)-DNA dG lesion eludes the nucleotide excision repair pathway better than diammineplatinum(lI)-DNA intrastrand d(GpG) cross-link. A factor that may be relevant to the difference is the influence of platination on DNA-mediated charge transfer. Atomic force microscopy is a method by which we can explore the possibility that phenanthriplatin influences charge transfer properties of DNA. Long DNA duplexes site-specifically modified with cisplatin or phenthanriplatin were prepared for AFM studies.