Synthesis of antisense oligonucleotides containing photocleavable protecting groups on the thymine bases and their photoinduced duplex formation.

Oligonucleotides containing photocleavable protecting groups at thymine bases were synthesized to induce the duplex formation by photo-irradiation. 6-Nitroveratryloxycarbonyl (NVOC) group was used for the photocleavable protecting group at N3 position of thymidine. An oligonucleotide containing NVOC groups (NVOC-ODN2:5'-dATG CAC CAT(NVOC) TCT(NVOC)GTC TGT-3') was synthesized by phosphoramidite method. The NVOC groups were found to be removable by UV irradiation at wavelength of 365 nm for 5 h. UV-melting temperature (Tm value) analysis indicated that the duplex of NVOC-ODN2 with the complementary RNA was significantly unstable compared with the unmodified DNA/RNA duplex (delta Tm=-13 degrees C). After UV irradiation at 365 nm, the Tm value of the mixture increased to the almost same as that of the unmodified duplex. These results suggest that the RNA binding ability of the NVOC-ODN2 can be induced by photocleavage of the NVOC groups.