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Yukiko Abe Last modified date:2020.01.22

Graduate School
Undergraduate School

Academic Degree
Master of Science (Pharmacy)
Country of degree conferring institution (Overseas)
Field of Specialization
Bioorganic and Synthetic Chemistry
Total Priod of education and research career in the foreign country
Research Interests
  • Development of specific recognition ligand for DNA damages
    keyword : specific recognition, DNA damages, ligand
  • Development of self-cleaving functional probe
    keyword : detection, specific recognition, catalytic cycle
Academic Activities
1. 阿部 由紀子, 佐々木 茂貴, DNA cleavage at the AP site via b-elimination mediated by the AP site-binding ligands, Bioorganic & Medicinal Chemistry, 24, 4, 910-914, 2016.01, DNA is continuously damaged by endogenous and exogenous factors such as oxidation and alkylation. In the base excision repair pathway, the damaged nucleobases are removed by DNA N-glycosylase to form the abasic sites (AP sites). The alkylating antitumor agent exhibits cytotoxicity through the formation of the AP site. Therefore blockage or modulation of the AP site repair pathway may enhance the antitumor efficacy of DNA alkylating agents. In this study, we have examined the effects of the nucleobase-polyamine conjugated ligands (G-, A-, C- and T-ligands) on the cleavage of the AP site. The G- and A-ligands cleaved DNA at the AP site by promoting β-elimination in a non-selective manner by the G-ligand, and in a selective manner for the opposing dT by the A-ligand. These results suggest that the nucleobase-polyamine conjugate ligands may have the potential for enhancement of the cytotoxicities of the AP site..
2. Yukiko Abe, Osamu Nakagawa, Rie Yamaguchi, Shigeki Sasaki, Synthesis and Binding Properties of New Selective Ligands for the Nucleobase Opposite the AP Site, Bioorganic & Medicinal Chemistry, 20, 11, 3470-3479, 2012.06, DNA is continuously damaged by endogenous and exogenous factors such as oxidative stress or DNA alkylating agents. These damaged nucleobases are removed by DNA N-glycosylase and form apurinic/apyrimidinic sites (AP sites) as intermediates in the base excision repair (BER) pathway. AP sites are also representative DNA damages formed by spontaneous hydrolysis. The AP sites block DNA polymerase and a mismatch nucleobase is inserted opposite the AP sites by polymerization to cause acute toxicities and mutations. Thus, AP site specific compounds have attracted much attention for therapeutic and diagnostic purposes. In this study, we have developed nucleobase-polyamine conjugates as the AP site binding ligand by expecting that the nucleobase part would play a role in the specific recognition of the nucleobase opposite the AP site by the Watson-Crick base pair formation and that the polyamine part should contribute to the access of the ligand to the AP site by a non-specific interaction to the DNA phosphate backbone. The nucleobase conjugated with 3,3’-diaminodipropylamine (A-ligand, G-ligand, C-ligand, T-ligand and U-ligand) showed a specific stabilization of the duplex containing the AP site depending on the complementary combination with the nucleobase opposite the AP site; i.e., A-ligand to T, G-ligand to C, C-ligand to G, T- and U-ligand to A. The thermodynamic binding parameters clearly indicated that the specific stabilization is due to specific binding of the ligands to the complementary AP site. These results have suggested that the complementary base pairs of the Watson-Crick type are formed at the AP site..
1. Yukiko Abe, Osamu Nakagawa, Rie Yamaguchi, Shigeki Sasaki, Selective stabilization of an abasic site by polyamine-nucleobase conjugates, 2010 International Chemical Congress of Pacific Basin Societies, 2010.12.
2. Yukiko Abe, Osamu Nakagawa, Rie Yamaguchi, Shigeki Sasaki, Formation of a Pseudo-Base Pair in an Abasic site in the Duplex DNA, 第37回 国際核酸化学シンポジウム, 2010.11.
Membership in Academic Society
  • The Chemical Society of Japan