Drug Discov Ther. 2007;1(1):65-72.

Investigation of the binding behaviors of isonucleoside-incorporated oligonucleotides with complementary sequences.

Guan Z, Jin HW, Yang ZJ, Zhang LR, Zhang LH

Oligonucleotides consisting of isonucleoside 2’,5’-anhydro-3’-nucleobase-D-mannitol incorporated in 1’→4’ linkage mode were synthesized. Their binding behaviors with complementary sequences were investigated via thermal denaturation and CD spectra. 6’ O-methyl-2’,5’-anhydro-3’-(thymin-1-yl)-D-mannitol incorporated oligonucleotide was also synthesized to investigate the effect of hydroxy groups of isonucleosides on duplex formation. The results showed that the 6’-OH free isonucleosidemodified oligonucleotide was able to form a B-like duplex with 3’→5’ complementary native oligodeoxynucleotide in the 1’→4’ direction. The free hydroxy group in the isonucleoside made a significant contribution to the affinity of the modified oligonucleotide to the complementary sequence, which was confirmed by molecular dynamics simulation.

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