Oligonucleotides containing 2′-O-methyl-5-(1-phenyl-1,2,3-triazol-4-yl)uridines demonstrate increased affinity for RNA and induce exon-skipping in vitro

A. Gimenez Molina; P. Raguraman; L. Delcomyn; R.N. Veedu; P. Nielsen

doi:10.1016/j.bmc.2021.116559

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Oligonucleotides containing 2′-O-methyl-5-(1-phenyl-1,2,3-triazol-4-yl)uridines demonstrate increased affinity for RNA and induce exon-skipping in vitro

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Peer reviewed

Oligonucleotides containing 2′-O-methyl-5-(1-phenyl-1,2,3-triazol-4-yl)uridines demonstrate increased affinity for RNA and induce exon-skipping in vitro

A. Gimenez Molina, P. Raguraman, L. Delcomyn, R.N. Veedu and P. Nielsen

Bioorganic & Medicinal Chemistry, Vol.55, Art. 116559

2022

DOI: https://doi.org/10.1016/j.bmc.2021.116559

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Abstract

The nucleotide monomer containing the 1-phenyl-1,2,3-triazole group attached to the 5-position of 2′-O-methyluridine is hereby presented together with a derivative further substituted with a p-sulfonamide group on the phenyl ring. Both were conveniently synthesised, and synergistic effect of the modifications were demonstrated when introduced into oligonucleotides and hybridised to complementary RNA. The combination of stacking of the phenyltriazoles and the conformational steering from the 2′-OMe group gave thermally very stable duplexes. Exon skipping in the distrophin transcript using 20-mer 2′-OMePS sequences with two phenyltriazoles introduced in different positions with and without the sulfonamide demonstrated efficient exon skipping but at the same level as the 2′-OMePS reference ASO.

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Title: Oligonucleotides containing 2′-O-methyl-5-(1-phenyl-1,2,3-triazol-4-yl)uridines demonstrate increased affinity for RNA and induce exon-skipping in vitro
Authors/Creators: A. Gimenez Molina (Author/Creator)
P. Raguraman (Author/Creator) - Murdoch University
L. Delcomyn (Author/Creator) - University of Southern Denmark
R.N. Veedu (Author/Creator) - Murdoch University
P. Nielsen (Author/Creator) - University of Southern Denmark
Publication Details: Bioorganic & Medicinal Chemistry, Vol.55, Art. 116559
Publisher: Elsevier Ltd.
Identifiers: 991005542883707891
Copyright: © 2021 Elsevier Ltd.
Murdoch Affiliation: Centre for Molecular Medicine and Innovative Therapeutics
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 2 Chemistry; 2.170 Nucleic Acids Chemistry; 2.170.988 Oligonucleotide Modifications
Web Of Science research areas: Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic
ESI research areas: Chemistry