Effects of the 2-substituted adenosine-1,3-diazaphenoxazine 5′-triphosphate derivatives on the single nucleotide primer extension reaction by DNA polymerase

Yosuke Taniguchi, Ikuko Sagara, Yusuke Nagata, Yoshiya Kikukawa, Shigeki Sasaki

Research output: Contribution to journalArticle

Abstract

The adenosine triphosphate derivatives of 2-oxo-1,3-diazaphenoxazine (dAdapTP) showed a significant discrimination ability for the template strand including that between 8-oxo-2′-deoxyguanosine (8-oxodG) and 2′-deoxyguanosine (dG) by the single nucleotide primer extension reaction using the Klenow Fragment. In this study, we synthesized new dAdapTP derivatives, i.e., 2-amino-dAdapTP, 2-chloro-dAdapTP and 2-iodo-dAdapTP, to investigate the effect on the selectivity and efficiency of incorporation for the primer extension reaction using a variety of DNA polymerases. In contrast to the previously tested dAdapTP, the selectivity and efficiency of the 2-halo-dAdapTP incorporation were dramatically decreased using the Klenow Fragment. Moreover, the efficiency of the 2-amino-dAdapTP incorporation into the T-containing template was almost the same with that of dAdapTP. In the case of the Bsu DNA polymerase, the efficiency of all the dAdapTP derivatives decreased compared to that using the Klenow Fragment. However, the incorporation selectivity of dAdapTP had improved against the oxodG-containing template for all the template sequences including the T-containing template. Moreover, 2-amino-dAdapTP showed a better efficiency than dAdapTP using the Bsu DNA polymerase. The 2-amino group of the adenosine unit may interact with syn-oxodG at the active site of the Bsu DNA polymerase during the single primer extension reaction.

Original languageEnglish
Pages (from-to)1123-1130
Number of pages8
JournalChemical and Pharmaceutical Bulletin
Volume67
Issue number10
DOIs
Publication statusPublished - Jan 1 2019

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Drug Discovery

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