Incorporation into DNA of nucleotides linked to functional groups has a variety of potential applications. Several organic reporter groups, covalently linked to nucleotides, are already widely used as experimental tools for nucleic acid modification.[1] Extensive studies on the synthesis, structure, and properties of metalated nucleotides, oligonucleotides, DNA, and RNA, mainly but not solely cisplatin related, have been reported. [2,3] Such metalation is generally achieved by direct reactions of the polynucleotide substrate with a metal complex.Herein, we report experimental evidence that a DNA polymerase can incorporate N7-platinated guanines to give platinated DNA. A new method to obtain site-specific metalation, by incorporating metal-modified nucleotides into the DNA, is proposed. The possibility of obtaining a metal, covalently linked to a nucleotide, in a specific position of a polynucleotide sequence is expected to present a wide range of applications, both pharmacological (for example, drug design) and technological (for example, DNA-templatebased production of metal arrays).[3]Herein we show, for the first time, that metalated purines can be inserted into DNA by DNA polymerases during an in vitro synthetic process (Scheme 1 A). In our experiments we used: 1) a model DNA polymerase, that is, Taq polymerase, and 2) a simple model molecule, namely, the complex [Pt-(dien)(N7-5'-dGTP)] (1; dien = diethylenetriamine, 5'-dGTP = 5'-(2'-deoxy)guanosine triphosphate; Scheme 1 B). Complex 1 was chosen because, as a result of the lack of labile chloride ligands, it is unable to give chelates, as in the case of similar cisplatin derivatives.[2-4] The insertion of platinated purine bases into the complementary DNA chain during a DNA synthetic process is shown by using two different experimental approaches.In the first experiment, we performed a primer extension assay using a synthetic DNA primer/template substrate (Figure 1 A). The presence of only one C residue between the 40 T and 40 G residues in the DNA template allowed Taq DNA polymerase to insert only one G in the newly synthesized complementary strand. We prepared two reaction mixtures, both containing the above DNA primer/template and the Taq DNA polymerase. Moreover, in one reaction the four standard triphosphate nucleotides, 5'-dNTP (dNTP = deoxynucleotide triphosphate), including a-[32 P]-dATP (dATP = deoxyadenosine triphosphate) were added, whereas in the other 5'-dGTP was substituted by a mixture of 1 and 5'-dGTP in about 95:5 ratio. Such a mixture was the product of the synthesis of 1 performed in the presence of a small excess of 5'-dGTP with respect to [PtCl(dien)]Cl.[5] Under these conditions, the introduction of Pt into the newly synthesized DNA chain is necessarily controlled by the polymerase. The results of the DNA polymerization process were visualized by autoradiography (Figure 1 B) after separation of the primer extension products by electrophoresis on 13 % (v/v) polyacrylamide gel.For both the mixture containing the standard 5'-dNTPs and that...