Development of antigene strategy by triplex forming oligonucleotides having artificial nucleoside analogues

2015 Fiscal Year Final Research Report

• Project/Area Number: 24689006
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Kyushu University
• Principal Investigator: TANIGUCHI YOSUKE 九州大学, 薬学研究科(研究院), 准教授 (00452714)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 核酸医薬 / アンチジーン核酸 / 人工核酸 / 遺伝子発現制御

Outline of Final Research Achievements

The triplex DNA formation against duplex DNA offers a potential basis for genome targeting technology and/or medicine with sequence specificity. In triplex DNA, the sequence-specificity is established via the formation of specific base triplets between a triplex forming oligonucleotide and a duplex DNA, however, there is no natural nucleoside which can recognize inverted sites. The application of the triplex formation is consequently limited to the homopurine-homopyrimidine region of a duplex DNA. We showed the design and synthesis of artificial nucleoside analogues for selective recognition of CG base pair to expand triplex-forming sequence. The 2’-deoxycytidine derivatives were shown to possess high selectivity and affinity toward CG base pair without being effected by neighboring bases. Furthermore, TFO bearing them was demonstrated to effectively inhibit gene expression in living cells.

Free Research Field

生物有機合成化学