Specificity of Light-Induced Covalent Adduct Formation between RuIIOligonucleotide Conjugates and Target Sequences for Gene Silencing Applications : Light-Induced Covalent Adducts for Gene Silencing Applications

Marcélis, Lionel;Surin, Mathieu;Lartia, Rémy;Moucheron, Cécile;Kirsch-De Mesmaeker, Andrée;et.al.
(2014) European Journal of Inorganic Chemistry — Vol. 2014, p. 3016-3022 (2014)

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  • Marcélis, Lionelorcid-logoUCLouvain
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  • Surin, Mathieu
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  • Lartia, Rémy
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  • Moucheron, Cécile
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  • Kirsch-De Mesmaeker, Andrée
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Abstract
Under irradiation, Ru–TAP (TAP = 1,4,5,8-tetraazaphenanthrene) complexes tethered to oligonucleotides (Ru–ODN) hybridized to their complementary target sequences produce irreversible adducts with guanine (G) bases. The interesting feature is that the G bases that react in the double strand (DS) topology belong exclusively to the complementary strand; thus, no G base of the Ru–ODN strand participates in the production of these adducts. This highly specific photoreaction in the DS topology is demonstrated by gel electrophoresis analyses of different duplex sequences in which the positions of the G bases are varied. Atomistic molecular modelling simulations indicate that this specificity is due to important steric constraints for the intrastrand adduct formation in the duplex. Luminescence lifetime measurements furnish more detailed information on these different duplex systems.
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Marcélis, L., Surin, M., Lartia, R., Moucheron, C., Defrancq, E., & Kirsch-De Mesmaeker, A. (2014). Specificity of Light-Induced Covalent Adduct Formation between RuIIOligonucleotide Conjugates and Target Sequences for Gene Silencing Applications : Light-Induced Covalent Adducts for Gene Silencing Applications. European Journal of Inorganic Chemistry, 2014, 3016-3022. https://doi.org/10.1002/ejic.201402189 (Original work published 2014)