Monofunctional trans-PtII(NH3)2 modification of pyrimidine-rich deoxyoligonucleotides:: direct platination and use of a protective group

Ways are studied to obtain pyrimidine-rich deoxyoligonucleotides (ON) (n = 4-8) which are monofunctionally modified with a trans-[Pt(NH3)(2)Cl](+) entity: (i) direct platination of the ON with trans-Pt(NH3)(2)Cl-2; (ii) platination with the monoaqua species trans-[Pt(NH3)(2)Cl(H2O)](+); (iii) platination with trans-Pt(NH3)(2)(1-MeT)Cl or trans-[Pt(NH3)(2)(1-MeT)(H2O)](+) containing the acid-labile protective group 1-MeT (1-MeT = 1-methylthymine anion). Reactions with the oligonucleotides are followed by H-1 NMR spectroscopy and HPLC and the products are characterized by ESI MS and H-1 NMR. It was the aim of this work to find ways of preparing monofunctionally (trans-Pt-II(NH3)(2)) modified ON on a large scale for potential application in the antisense technology. (C) 1998 Elsevier Science S.A.