Title: Improved hybridisation potential of oligonucleotides comprising O-methylated anhydrohexitol nucleoside congeners
Authors: Van Aerschot, Arthur ×
Meldgaard, M
Schepers, Guy
Volders, F
Rozenski, Jef
Busson, Roger
Herdewijn, Piet #
Issue Date: Oct-2001
Publisher: Oxford univ press
Series Title: Nucleic acids research vol:29 issue:20 pages:4187-4194
Abstract: The hybridising potential of anhydrohexitol nucleoside analogues (HNAs) is well documented, but tedious synthesis of the monomers hampers their development. In a search for better analogues, the synthesis of two new methylated anhydrohexitol congeners 1 and 2 was accomplished and the physico-chemical properties of their respective oligomers were evaluated. Generally, oligonucleotides (ONs) containing the 3'-O-methyl derivative 1 showed a small increase in thermal stability towards complementary sequences as compared to HNA. Compared to the altritol modification, 3'-O-methylation seems to cause a small decrease in thermal stability of duplexes, especially when targeting RNA. These results suggest the possibility of derivatisation of the 3'-hydroxyl group of altritol-containing congeners without significantly affecting the thermal stability of the duplexes. The methyl glycosidic analogues 2 likewise increased the affinity for RNA in comparison with well-known HNA, while at the same time being economically more favorable monomers. However, homopolymers of 2 displayed self-pairing, but not so homopolymers of 1. Upon incorporation of the hexitols within RNA sequences in an effort to induce a beneficial pre-organised structure, the positive effect of the 3'-O-methyl derivative 1 proved larger than that of 2.
ISSN: 0305-1048
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Medicinal Chemistry (Rega Institute)
× corresponding author
# (joint) last author

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