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

Van Aerschot, A Meldgaard, M Schepers, G Volders, F Rozenski, J Busson, R Herdewijn, P

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

29

INGLESE

Article

Biochemistry & Biophysics

NUCLEIC ACIDS RESEARCH

0305-1048 → ACNP

29

20

2001

4187 - 4194

ISI

0305-1048(20011015)29:20<4187:IHPOOC>2.0.ZU;2-3

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.