Studies on the mechanism of DNA sequence selective alkylation by kapurimycin A3 analogs

Nucleic Acids Symp Ser. 1997:(37):27-8.

Abstract

We synthesized kapurimycin A3 ABCD-ring analog and compared the sequence selectivity for DNA guanine alkylation with those of kapurimycin A3 and ABC-ring analog. In the binding to DNA, it was shown by DNA unwinding assay that ABCD-ring analog binds tightly to DNA by intercalation into DNA duplex. DNA alkylation by ABCD-ring analog was sequence selective with an order of G*G > G*A > G*T > G*C. ABCD-ring analog has a stronger binding ability, a higher reactivity to DNA and a higher GG sequence selectivity in DNA alkylation than those to ABC-ring analog. The aromatic ring system plays an important role in the effective GG selective alkylation.

MeSH terms

  • Alkylation
  • Anthracenes / chemical synthesis*
  • Anthracenes / chemistry
  • Anthracenes / pharmacology
  • Antibiotics, Antineoplastic / chemical synthesis*
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology
  • Base Sequence
  • Binding Sites
  • DNA / chemistry*
  • Molecular Structure
  • Oligodeoxyribonucleotides / chemistry
  • Pyrones / chemical synthesis*
  • Pyrones / chemistry
  • Pyrones / pharmacology

Substances

  • Anthracenes
  • Antibiotics, Antineoplastic
  • Oligodeoxyribonucleotides
  • Pyrones
  • kapurimycin A3
  • DNA