Modulation of the B-A transition of DNA by potential antitumor antibiotics. Influence of the base composition of DNA.
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.
Fritzsche
H
H
Department of Biophysical Chemistry, Academy of Sciences, Jena, GDR.
Rupprecht
A
A
D000903:Antibiotics, Antineoplastic / Q000378:metabolism* / Q000494:pharmacology; D001482:Base Composition; D004247:DNA / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004269:DNA, Bacterial / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007364:Intercalating Agents / Q000378:metabolism / Q000494:pharmacology; D009690:Nucleic Acid Conformation; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D004269:DNA, Bacterial; D007364:Intercalating Agents; D004247:DNA