Selective Photo-Cross-Linking of 2′-O-Psoralen-Conjugated Oligonucleotide with Rnas Having Point Mutations

Abstract

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 a new type of anticancer drugs. In this report, we present a new type of antisense molecule that photo-cross-links to an oligoribonucleotide having a point mutation site in a sequence specific manner. 2′-O-psoralen-conjugated adenosine was synthesized in four steps from adenosine and introduced in the middle of an oligodeoxyribonucleotide (2′-Ps-oligo). Compared with 5′-O-psoralen-conjugated oligodeoxyribonucleotide (5′-Ps-oligo), which has a psoralen at the 5′-end, 2′-Ps-oligo more selectively photo-cross-linked to a pyrimidine base of the site of alteration from purine to pyrimidine in the oligoribonucleotide.

Keywords:

• Antisense oligonucleotide
• psoralen
• photo-cross-linking
• ras
• Point mutation

Acknowledgments

This research was partly supported by Grants for Regional Science and Technology Promotion (AM) from the Ministry of Education, Science, Sports and Culture of Japan and by a Grant for Feasibility Study from Innovation Plaza Kyoto. The authors are also indebted to Otsuka Pharmaceutical Co., Ltd. for their financial support.

Notes

*APs = 2′-O-psoralen-conjugated adenosine.