Modulation of the B-A transition of DNA by potential antitumor antibiotics. Influence of the base composition of DNA

J Biomol Struct Dyn. 1990 Apr;7(5):1135-40. doi: 10.1080/07391102.1990.10508551.

Abstract

The B-A transition of DNA in oriented films of DNA-drug complexes is more or less restricted as a consequence of drug binding as revealed by infrared linear dichroism. A fraction of DNA is irreversibly locked into the B form. This behavior is described by the number of DNA base pairs "frozen" in the B form by one drug molecule. This quantity is dependent on the DNA sequence the drug is attached to. In this paper, drug complexes of oriented films of NaDNA with a GC content of 42% from calf thymus and a GC-rich DNA from Micrococcus lysodeikticus were compared. The restriction of the B-A transition of DNA complexes with two intercalating antibiotics, aclacinomycin A and violamycin BI, is not severely influenced by the base composition of DNA. By contrast, the strong groove binding oligopeptide antibiotics netropsin and distamycin A are much less effective to restrict the B-A transition of GC-rich DNA than of AT-rich DNA. This finding is in agreement with previous results by other methods which support a model based upon a strong preference of AT clusters by these two non-intercalating drugs.

Publication types

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

MeSH terms

  • Antibiotics, Antineoplastic / metabolism*
  • Antibiotics, Antineoplastic / pharmacology
  • Base Composition
  • DNA / drug effects*
  • DNA / metabolism
  • DNA / ultrastructure
  • DNA, Bacterial / drug effects
  • DNA, Bacterial / metabolism
  • DNA, Bacterial / ultrastructure
  • Intercalating Agents / metabolism
  • Intercalating Agents / pharmacology
  • Nucleic Acid Conformation
  • Structure-Activity Relationship

Substances

  • Antibiotics, Antineoplastic
  • DNA, Bacterial
  • Intercalating Agents
  • DNA