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Incorporation of two modified nucleosides allows selective platination of an oligonucleotide making it suitable for duplex cross-linking

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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.

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Acknowledgements

This work was supported by funds from the Ministerio de Educación y Ciencia (grant CTQ2004-8275-C02-01) and the Generalitat de Catalunya (2005SGR-693 and Centre de Referència de Biotecnologia).

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Authors and Affiliations

  1. Departament de Química Orgànica, Facultat de Química, Universitat de Barcelona, Martí i Franquès 1-11, 08028, Barcelona, Spain

    Berta Algueró, Enrique Pedroso, Vicente Marchán & Anna Grandas

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  1. Berta Algueró
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  2. Enrique Pedroso
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  3. Vicente Marchán
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  4. Anna Grandas
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Correspondence to Vicente Marchán or Anna Grandas.

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Algueró, B., Pedroso, E., Marchán, V. et al. Incorporation of two modified nucleosides allows selective platination of an oligonucleotide making it suitable for duplex cross-linking. J Biol Inorg Chem 12, 901–911 (2007). https://doi.org/10.1007/s00775-007-0243-9

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  • DOI: https://doi.org/10.1007/s00775-007-0243-9

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