Synthesis of antisense oligonucleotides containing 2'-O-psoralenylmethoxyalkyl adenosine for photodynamic regulation of point mutations in RNA.

2'-O-psoralen-conjugated antisense oligonucleotide was able to recognize a point mutation of mRNA. It had outstanding ability to photo-cross-link only to oligoribonucleotides (ORN) having a point mutation. This type of antisense molecule is the only one of its kind so far. To give high photo-cross-linking efficiency and sequence selectivity to antisense molecules, we synthesized novel photo-reactive oligonucleotides (2'-Ps-xom) containing psoralen at the 2'-O-position adenosine via an ethoxymethylene (2'-Ps-eom), propoxymethylene (2'-Ps-pom) and butoxymethylene (2'-Ps-bom) linker, respectively. We evaluated the photo-cross-linking efficiency and sequence selectivity in photo-cross-linking of 2'-Ps-xom to the complementary ORN and to an ORN having a mismatch base. Among them, 2'-Ps-eom exhibited superior photo-cross-linking efficiency with high sequence selectivity.