Improved hybridisation potential of oligonucleotides comprising O-methylated anhydrohexitol nucleoside congeners

Citation
A. Van Aerschot et al., Improved hybridisation potential of oligonucleotides comprising O-methylated anhydrohexitol nucleoside congeners, NUCL ACID R, 29(20), 2001, pp. 4187-4194
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
NUCLEIC ACIDS RESEARCH
ISSN journal
0305-1048 → ACNP
Volume
29
Issue
20
Year of publication
2001
Pages
4187 - 4194
Database
ISI
SICI code
0305-1048(20011015)29:20<4187:IHPOOC>2.0.ZU;2-3
Abstract
The hybridising potential of anhydrohexitol nucleoside analogues (HNAs) is well documented, but tedious synthesis of the monomers hampers their develo pment. In a search for better analogues, the synthesis of two new methylate d anhydrohexitol congeners 1 and 2 was accomplished and the physico-chemica l properties of their respective oligomers were evaluated. Generally, oligo nucleotides (ONs) containing the 3'-O-methyl derivative I showed a small in crease 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 targeti ng RNA. These results suggest the possibility of derivatisation of the 3'-h ydroxyl group of altritol-containing congeners without significantly affect ing 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. Howeve r, homopolymers of 2 displayed self-pairing, but not so homopolymers of 1. Upon incorporation of the hexitols within RNA sequences in an effort to ind uce a beneficial pre-organised structure, the positive effect of the 3'-O-m ethyl derivative 1 proved larger than that of 2.