The Binding of the Carcinostatic Drugs Cis-[Pt(NH3)2Cl2] and [Ru(NH3)5Cl]Cl2 with Yeast Transfer RNAPhe. Absence or Binding to Watson-Crick Base Pairs

Abstract

Cis-diammedichloroplatinum(II) is a potent anticancer agent and is widely used in clinical work (1). On the other hand, the transdiammine-dichloroplatinum(II) is inactive (2). A search for related platinum group metal containing oncostatic drugs has led to the discovery of the pentaammineruthenium(III) complex which also inhibits cellular DNA synthesis in a manner (3) similar to cis-[Pt(NH3)2C12] Solution studies have shown that the guanine bases of DNA are preferentially attacked by the Pt drug at low drug to DNA ratios (4). The lack of oncostatic activity of the trans-Pt has led to the suggestion that the cis-Pt exerts its activity by forming intrastrand crosslinks between adjacent guanines on the DNA chain (5). This mode of complexation has received some support from solution studies of polynucleotides (6) and single-crystal X-ray studies of cis-Pt complexes with nucleic acid constituents (7–9). A competing model for the intrastrand cross-linked model is the bidentate coordinaton of the cis-Pt to the N(7) and keto 0(6) atoms of guanines. Neither complexation mode is possible for trans-Pt. We have carried out a crystallographic investigation of the interaction of both the cis-Pt, and the trans-Pt as well as the [Ru(HN3)5]3+ ion with yeast phenylalanine transfer ribonucleic acid (tRNAPhe) to provide further in ghts on the nature of the interaction of these metal complexes. tRNAPhe is a good system since its structure is known and crystals suitable for X-ray diffraction studies can be obtained with little difficulty. The main drawback, however, is that tRNA is in some ways different from DNA and therefore the results obtained should be extrapolated to DNA with caution.