Synthesis of new functionalized nucleic acids by the pentaerythritol linker.

• Project/Area Number: 13470481
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: HOKKAIDO UNIVERSITY
• Principal Investigator: MATSUDA Akira Hokkaido Univ., Grad. School of Pharm. Sci., Prof., 大学院・薬学研究科, 教授 (90157313)
• Project Period (FY): 2001 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥9,300,000 (Direct Cost: ¥9,300,000); Fiscal Year 2002: ¥3,200,000 (Direct Cost: ¥3,200,000); Fiscal Year 2001: ¥6,100,000 (Direct Cost: ¥6,100,000)
• Keywords: pentaerythritol / antigene / triple helix / hydrogen bond / Hoogsteen / reverse Hoogsteen / thermal stability / foot printing / アントラキノン

Research Abstract

The 3'-3'-linked oligodeoxynucleotides (ODNs) by pentaerythritol with an intercalator at the junction point is that can form the parallel triplexes with the duplex target by Hoogsteen hydrogen bonds were synthesized. Stability of the triplexes with the target duplexes was studied by thermal denaturation. The 3'-3'-linked ODNs with the anthraquinonyl group enhanced the thermal stability of the triplexes when compared with those without the intercalator and the unmodified nonamer. It was found that the ODNs carrying the anthraquinonyl groups can form thermally stable triplexes by skipping two or three extra base pairs between two binding domains of the target duplexes. The 3'-3'-linked ODN with the anthraquinonyl group at the junction point inhibited the cleavage by the enzyme Hind III more effectively.
We also synthesized the 3'-3'-linked TFOs that can form the antiparallel triplexes with the duplex DNA target by reverse Hoogsteen hydrogen bonds. The alternate-strand triplexes were significantly stabilized by linking the TFO fragments with the pentaerythritol linker. And, unlike the alternate-strand triplexes composed of the pyrimidine motif, the terminal ammonium ion of the aminobutyl-linker and the intercalator of the TFOs did not contribute to the stability of the alternate-strand triplex comprised of the purine motif.

Research Products

• [Publications] Ueno, Y., et al.: "Alternate-strand triple-helix formation by the 3'-3'-linked oligodeoxynucleotides with the anthraquinonyl group at the junction point"Bioconjugate Chem.. 12. 635-642 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ueno, Y., et al.: "Alternate-stand triple-helix formation by the 3'-3'-linked oligodeoxynucleotides with the anthraquinonyl group at the junction point"Nucleic Acids Res.. Suppl.1. 11-12 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ueno, Y., et al.: "Synthesis of the 3'-3'-linked oligonucleotides branched by the pentaerythritol linker and the thermal stabilities of the triplexes with the single stranded DNA or RNA"Bioconjugate Chem.. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hoshida, S., et al.: "Alternate-strand triple-helix formation by the 3'-3'-linked oligodeoxynucleotides using a purine motif"Bioconjugate Chem.. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ueno, Y., Mikawa, M., Hoshika, S., Matsuda, A.: "Alternate-strand triple-helix formation by the 3'-3'-linked oligodeoxynucleotides with the anthraquinonyl group at the junction point"Bioconjugate Chem.. 12. 635-642 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ueno, Y., Mikawa, M., Hoshika, S., Takeba, M., Kitade, Y., Matsuda, A.: "Alternate-strand triple-helix formation by 3'-3'-linked oligodeoxynucleotides with the intercalators at the junction point"Nucleic Acids Res.. Suppl.1. 11-12 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ueno, Y. Shibata, A., Matsuda, A, Kitade, Y.: "Synthesis of the 3'-3'-linked oligonucleotides branched by the pentaerythritol linker and the thermal stabilities of the triplexes with the single stranded DNA or RNA"Bioconjugate Chem.. in press.
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hoshika, S., Ueno, Y., Matsuda, A.: "Alternate-strand triple-helix formation by the 3'-3'-linked oligodeoxynucleotides using a purine motif"Bioconjugate Chem.. in press.
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hoshika, S. et al.: "Alternate-strand triple-helix formation by the 3'-3'-linked oligodeoxynucleotides using a purine motif"Bioconjugate Chem.. (in press). (2002)
• [Publications] Ueno, Y et al.: "Synthesis of 3'-3'-linked oligonucleotides branched by a pentaerythritol inker and the thermal stabilities of the triplexes with single-stranded DNA or RNA."Bioconjugate Chem.. (in press). (2002)
• [Publications] Ueno, Y., et al.: "Alternate-strand triple-helix formation by the 3'-3'-linked oligodeoxynucleotides with the anthraquinonyl group at the junction point"Bioconjugate Chem.. 12. 635-642 (2001)
• [Publications] Ueno, Y., et al.: "Alternate-strand triple-helix formation by 3'-3'-linked oligodeoxynucleotides with the intercalators at the junction point"Nucleic Acids Res.. Suppl. 1. 11-12 (2001)