DNA cleavage at the AP site via β-elimination mediated by the AP site-binding ligands

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)910-914
Number of pages5
JournalBioorganic and Medicinal Chemistry
Volume24
Issue number4
DOIs
Publication statusPublished - Feb 15 2016

Fingerprint

DNA Cleavage
Binding Sites
Ligands
DNA
Alkylating Agents
Polyamines
Cytotoxicity
Repair
DNA Glycosylases
Alkylation
DNA Repair
Antineoplastic Agents
Modulation
Oxidation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

DNA cleavage at the AP site via β-elimination mediated by the AP site-binding ligands. / Abe, Yukiko S.; Sasaki, Shigeki.

In: Bioorganic and Medicinal Chemistry, Vol. 24, No. 4, 15.02.2016, p. 910-914.

Research output: Contribution to journalArticle

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