DNA binding activity and inhibition of DNA-protein interactions. Differential effects of tetra-p-amidino-phenoxyneopentane and its 2'-bromo derivative

Biochem Pharmacol. 1992 Nov 17;44(10):1985-94. doi: 10.1016/0006-2952(92)90101-n.

Abstract

In the present study are reported the differential DNA binding activity of the anti-tumor polyamidine tetra-p-amidinophenoxyneopentane (TAPP-H) and its 2'-halo derivative (TAPP-Br), and their effects on the binding of the recombinant Epstein-Barr virus (EBV) nuclear antigen to a synthetic oligonucleotide mimicking the target DNA sequence present in the EBV genome. In addition, the proliferation kinetics and cell cycle analysis of human leukemia K562 cells treated with TAPP-H and TAPP-Br are reported. The possible in vivo relationship between DNA binding affinity and cytotoxicity is also discussed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Viral / chemistry
  • Antigens, Viral / metabolism*
  • Base Sequence
  • Benzamidines / pharmacology*
  • Cell Cycle
  • Cell Division / drug effects
  • DNA, Viral / metabolism*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Diminazene / analogs & derivatives
  • Diminazene / pharmacology
  • Dose-Response Relationship, Drug
  • Epstein-Barr Virus Nuclear Antigens
  • Humans
  • Molecular Sequence Data
  • Tumor Cells, Cultured / drug effects

Substances

  • Antigens, Viral
  • Benzamidines
  • DNA, Viral
  • DNA-Binding Proteins
  • Epstein-Barr Virus Nuclear Antigens
  • 1,3-di-(4-amidinophenoxy)-2,2-bis-(4-amidinophenoxymethyl)propane
  • 4,4'-(2,2-bis((4-(aminoiminomethyl)-2-bromophenoxy)methyl)-1,3-propanediyl)bis(oxy))bis(3-bromobenzenecarboximidamide
  • diminazene aceturate
  • Diminazene