title: Incorporation of two modified nucleosides allows selective platination of an oligonucleotide making it suitable for duplex cross-linking.
abstract: Platinated oligonucleotides are promising tools for the control of gene expression, since they may target and cross-link nucleic acid chains. Here we describe a method for the preparation of platinated oligonucleotides that has proved able to selectively cross-link complementary sequences, making use of 5-methylcytidine analogs with thioether or imidazole groups attached to the 4-position. These nucleoside analogs were derivatized as phosphoramidites and introduced in oligonucleotide chains using standard phosphite triester chemistry. Different oligonucleotide sequences containing either one or two analogs appending from the 5'-end were synthesized and used in preliminary platination studies. The reaction of transplatin with oligonucleotides containing the thioether-modified nucleobase was fast, but generally afforded unstable adducts and complex reaction mixtures. The imidazole-containing oligonucleotides reacted with transplatin much more slowly, in particular at slightly basic pH, and it was found that the imidazole-modified cytosine was less reactive than the natural nucleobases. In contrast, transplatin selectively reacted with the thioether and imidazole groups of oligonucleotides containing the two cytosine analogs in neighboring positions, even in the presence of the four nucleobases and particularly three guanines, affording platinated oligonucleotides suitable for cross-linking.
authors.affiliation: Departament de Química Orgànica, Facultat de Química, Universitat de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain.
authors.forename: Berta
authors.initials: B
authors.lastname: Algueró
authors.forename: Enrique
authors.initials: E
authors.lastname: Pedroso
authors.forename: Vicente
authors.initials: V
authors.lastname: Marchán
authors.forename: Anna
authors.initials: A
authors.lastname: Grandas
mesh_terms: D002945:Cisplatin / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000138:chemical synthesis*; D003562:Cytidine / Q000031:analogs & derivatives / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry; D009705:Nucleosides / Q000138:chemical synthesis*; D009841:Oligonucleotides / Q000138:chemical synthesis*; D017671:Platinum Compounds / Q000737:chemistry; D013440:Sulfides / Q000737:chemistry
chemical_list: D003432:Cross-Linking Reagents; D007093:Imidazoles; D009705:Nucleosides; D009841:Oligonucleotides; D017671:Platinum Compounds; D013440:Sulfides; C034697:transplatin; D003562:Cytidine; D002945:Cisplatin; C016568:5-methylcytidine