A1 Refereed original research article in a scientific journal
Oligonucleotide-Palladacycle Conjugates as Splice-Correcting Agents
Authors: Hande M, Saher O, Lundin KE, Smith CIE, Zain R, Lonnberg T
Publisher: MDPI
Publication year: 2019
Journal: Molecules
Journal name in source: MOLECULES
Journal acronym: MOLECULES
Article number: ARTN 1180
Volume: 24
Issue: 6
Number of pages: 13
ISSN: 1420-3049
DOI: https://doi.org/10.3390/molecules24061180
Web address : https://www.mdpi.com/1420-3049/24/6/1180
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/40243664
2'-O-Methylribo phosphorothioate oligonucleotides incorporating cyclopalladated benzylamine conjugate groups at their 5'-termini have been prepared and their ability to hybridize with a designated target sequence was assessed by conventional UV melting experiments. The oligonucleotides were further examined in splice-switching experiments in human cervical cancer (HeLa Luc/705), human liver (HuH7_705), and human osteosarcoma (U-2 OS_705) reporter cell lines. Melting temperatures of duplexes formed by the modified oligonucleotides were approximately 5 degrees C lower than melting temperatures of the respective unmodified duplexes. The cyclopalladated oligonucleotides functioned as splice-correcting agents in the HeLa Luc/705 cell line somewhat more efficiently than their unmodified counterparts. Furthermore, the introduction of this chemical modification did not induce toxicity in cells. These results demonstrate the feasibility of using covalently metalated oligonucleotides as therapeutic agents.
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