Selective regulation of mutant K-ras mRNA expression by photo-cross-linking antisense oligonucleotide.
It has been reported that point mutations in genes are responsible for various cancers and the selective regulation of the gene expression is an important issue to develop new types of anticancer drugs. In this report, we report new types of antisense molecules that photo-cross-link to target mRNA having a point mutation site in a sequence specific manner. We designed and synthesized photo-reactive antisense oligonucleotides containing a 2'-O-psoralen-conjugated adenosine (2'-Ps-oligo). They contain a psoralen via an ethoxymethylene linker (2'-Ps-eom), a propoxymethylene linker (2'-Ps-pom) and a buthoxymethylene linker (2'-Ps-bom), respectively. We evaluated the photo-cross-linking efficiency and the sequence specificity toward complementary RNA. 2'-Ps-eom showed the highest photo-cross-linking efficiency among 2'-Ps-oligos.
Higuchi
Maiko
M
Department of Biomolecular Engineering, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto606-8585, Japan.
Yamayoshi
Asako
A
Kobori
Akio
A
Murakami
Akira
A
D000241:Adenosine / Q000737:chemistry; D011564:Furocoumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000528:radiation effects; D005786:Gene Expression Regulation; D011905:Genes, ras; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000528:radiation effects*; D017354:Point Mutation; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays
D011564:Furocoumarins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D000241:Adenosine