INTERACTIONS OF PLATINUM AMINE COMPOUNDS WITH SULFUR-CONTAINING BIOMOLECULES AND DNA FRAGMENTS

This chapter presents a discussion on the interactions of platinum amine biomolecules and DNA fragments compounds with sulfur-containing biomolecules and DNA fragments. From the past, cis-diamminedichloroplatinum(II) has emerged as the classic compound in the context of antitumor drug therapy. Because it is generally accepted that binding of the compound to DNA is a major requirement for its biological activity, scientists have focused their attention especially on platinum-DNA interactions. The chapter discusses the latest results concerning these interactions. The chapter focuses on the reactions of this and related platinum compounds with S-containing biomolecules. Such interactions are considered to have an overall inhibitory effect on the drug action and are, therefore, of considerable importance. Besides cis-Pt other platinum compounds have been synthesized and tested for antitumor activity, obtaining higher solubility, better antitumor activity, and lower toxicity. The synthesis of most of these platinum compounds is largely governed by two empirical rules, concerning the trans-labilizing power of the coordinated ligands and the difference in platinum-ligand bond strength. Because platinum is a class B metal, it should be expected that platinum compounds show relatively high affinity for nitrogen donor sites in DNA—that is, the nucleobases rather than for the phosphate-deoxyribose moiety. © 1991 Academic Press Inc.