DEVELOPMENT OF NOVEL SPIN-LABELED NUCLEOSIDES

• Project/Area Number: 13672220
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Kyushu University
• Principal Investigator: ASO Mariko Faculity of Pharm. Assistant, 大学院・薬学研究院, 助手 (30201891)
• Co-Investigator(Kenkyū-buntansha): SUEMUNE Hiroshi Faculty of Pharm. Prof., 大学院・薬学研究院, 教授 (20095897)
• Project Period (FY): 2001 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥4,100,000 (Direct Cost: ¥4,100,000); Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000); Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
• Keywords: Spin-labeled nucleoside / N-tert-butylaminoxyl / radical / N-tert-butylaminoxyl

Research Abstract

We designed a new type of spin-labeled nucleosides with an N-tert-butyl aminoxyl raical which is introduced to nucleobase directly. Purine and pyrimidine nucleosides with aminoxyl radical were synthesized to investigate stability and behavior of N-tert-butyl aminoxyl radical on nucleobase.
1) EPR spectra of 6-N-tert-butyl aminoxyl uridine (1a) and 6-N-tert-butyl aminoxyl cytidine (2a) were measured. The aN value of 2a decreased in the presence of 10 equiv. of guanosine derivatives (12.7 gauss) compared to that of 2a itself (13 gauss).
2) In order to study EPR spectra of oligonucleotide containing 2'-deoxy 6-N-tert-butyl aminoxyl uridine (4), 3, the precursor of radical, was incorporated into 15-mer. Unfortunately, the Tm value of 15-mer containing 3 decreased considerably compared to natural type 15-mer and EPR studies of 4 containing oligonucleotide were not done.
3) We planned to synthesis of 2'-deoxy 5-N-tert-hydroxylamino uridine (5) and 2-N-tert-hydroxylamino inosine (6), which might have anti conformation and their incorporation into oligonucleotide might not disturb stable duplex formation. We successfully synthesized 5 via metal halogen exchange reaction of 2'-deoxy 5-iodouridine sodium salts. We also synthesized 6.

Research Products

• [Publications] M.Aso et al.: "Molecular design of a new class of spin-labeled ribonucleosides with N-tert-butyl arminoxyl radicals"J.Org.Chem.. 66. 3513-3520 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] M.Aso et al.: "Synthesis and properties of a new class of nucleosides with spin source"Nucleic Acids Research Supplement. 1. 115-116 (2001)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] M.Aso et al.: "Synthesis and Properties of N-t-butylaminoxyl Nucleosides"Nucleic Acids Research Supplement. 139-140 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] M.Aso et al.: "A simple and efficient method for synthesis of 5-substituted 2'-deoxy-uridine nucleosides using metal-halogen exchange reaction of 5-iodo-2'-deoxyuridine sodium salt"Chem.Commun.. 1094-1095 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] M. Aso et al.: "Molecular design of a new class of spin-labeled ribonucleosides with N-tert-butyl aminoxyl radicals"J. Org. Chem. 66. 35113-3520 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] M. Aso et al.: "Synthesis and properties of a new class of nucleosides with spin source"Nucleic Acids Research Supplement. 1. 115-116 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] M. Aso et al.: "Synthesis and Properties of N-t-butylaminoxyl Nucleosides"Nucleic Acids Research Supplement. 2. 139-140 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] M. Aso et al.: "A simple and efficient method for synthesis of 5-substituted 2'-deoxy-uridine nucleosides using metal-halogen exchange reaction of 5-iodo-2'-deoxyuridine sodium salt"Chem. Commun. 1094-1095 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] M.Aso et al.: "Synthesis and Properties of N-t-butylaminoxyl Nucleosides"Nucleic Acids Research Supplement. 2. 139-140 (2002)
• [Publications] M.Aso et al.: "A simple and efficient method for synthesis of 5-substituted 2'-deoxyuridine nucleosides using metal-halogen exchange reaction of 5-iodo-2'-deoxyuridine sodium salt"Chemical Communications. (accepted).
• [Publications] M.Aso et al.: "Molecular design of a new class of spin-labeled ribonucleosides with N-tert-butyl aminoxyl radicals"J. Org. Chem.. 66(10). 3513-3520 (2001)
• [Publications] M.Aso et al.: "Synthesis and properties of a new class of nucleosides with spin source"Nucleic Acids Research Supplement. 1. 115-116 (2001)