A non-classical intercalation model for a bleomycin amplifier

Anticancer Drug Des. 1988 Mar;2(4):387-98.

Abstract

The bleomycin amplifier 1 is sterically hindered and twisted about the torsional bond joining the two aromatic rings. The intercalation of 1 and its sterically unhindered isomer 2 with DNA has been studied using n.m.r., viscometric titrations of superhelical and linear DNA, and flow dichroism. Based on the unusually strong interaction of 1 with DNA base pairs, a non-classical intercalation model for this compound is proposed. The intrinsic twists of both the unfused biaromatic system of 1 and the hydrogen-bonded DNA base pairs are retained in the intercalator-DNA complex, and the methyl group of 1 is accommodated between the hydrogen bonded bases. The complex of 1 is the first example found to date of this type of intercalation of the methyl group with DNA. The structure-activity relationships as bleomycin amplifiers for 1, 2 and similar derivatives is discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bleomycin / pharmacology*
  • DNA / metabolism
  • Intercalating Agents / pharmacology*
  • Models, Structural
  • Nucleic Acid Conformation
  • Structure-Activity Relationship

Substances

  • Intercalating Agents
  • Bleomycin
  • DNA