Oligonucleotides platinum

Oligomers, condensation, in formation of hy-droxo-bridged complexes, 32 91 Oligonucleotides, platinum binding, 37 185-187... 

After this brief introduction, the chapter will focus on solvolysis reactions and acid-base equilibria of various platinum compounds and on species distribution of isomeric [PtCl2(NH3)2] in aqueous solution in Section 2. Binding of platinum compounds to monomeric nucleobase derivatives will be discussed in Section 3, while Section 4 pays attention to the reactions of Pt-nucleobase complexes with different nucleophiles. And finally, the interactions of Pt with DNA and defined oligonucleotides will be discussed in Section 5. 

In general, covalent coordination of platinum to phosphate groups has been neglected at the oligonucleotide level, although such interaction is feasible and has been observed with phosphate anions [109]. In N,N-di-methylformamide, ds-DDP seems to be able to coordinate to the phos-phodiester groups of d(TpT) and d(TpG)" [110]. In the case ofd(TpT)-,... 

Rate constants for reaction of cis-[Pt(NH3)2(H20)Cl]+ with phosphate and with S - and 5/ -nucleotide bases are 4.6xl0-3, 0.48, and 0.16 M-1s-1, respectively, with ring closure rate constants of 0.17 x 10 5 and 2.55x10-5s-1 for subsequent reaction in the latter two cases 220). Kinetic aspects of interactions between DNA and platinum(II) complexes such as [Pt(NH3)3(H20)]2+, ds-[Pt(NH3)2(H20)2]2+, and cis-[Pt(NH3)2(H20)Cl]+, of loss of chloride from Pt-DNA-Cl adducts, and of chelate ring formation of cis-[Pt(NH3)2(H20)(oligonucleotide)]"+ intermediates implicate cis-[Pt(NH3)2(H20)2]2+ rather than cis-[Pt(NH3)2 (H20)C1]+, as usually proposed, as the most important Pt-binder 222). The role of aquation in the overall scheme of platinum(II)/DNA interactions has been reviewed 223), and platinum(II)-nucleotide-DNA interactions have been the subject of molecular modeling investigations 178). 

Polymer-coated stents have been used successfully to deliver micromolar concentrations of c-myc antisense PMO into the vessel wall (74) (Fig, 2). Zhang et al. (75) reported effective local delivery of c-myc antisense ODN by gelatin-coated platinum-ipidium stents in rabbits. These experiences showed that ultimate success will require polymers that are capable of rapid elution of the oligonucleotide with minimal capacity to inflame or otherwise cause additional injury to the vessel wall. 

Zhang XX, Cui CC, Xu XG, Hu XS, Fang WH, Kuang BJ. In vivo distribution of c-myc antisense oligonucleotides local delivered by gelatin-coated platinum-iridium stent in rabbits and its effect on apoptosis. Chin MedJ (Engl) 2004 I 17(2) 258-263. 

---