The 2-amino group of guanine is absolutely required for specific binding of the anti-cancer antibiotic echinomycin to DNA

The 2-amino group of guanine is believed to be a critical determinant of potential DNA binding sites for echinomycin and related quinoxaline antibiotics. In order to probe its importance directly we have studied the interaction between echinomycin and DNA species in which guanine N(2) is deleted by...

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Bibliographic Details
Published in:Nucleic acids research 1992-11, Vol.20 (21), p.5601-5606
Main Authors: Marchand, Christophe, Bailly, Christian, McLean, Michael J., Moroney, Simon E., Waring, Michael J.
Format: Article
Language:English
Subjects:
Antineoplastic agents
Base Sequence
Binding Sites
Biological and medical sciences
Deoxyribonuclease I
DNA - chemistry
DNA - metabolism
Echinomycin - metabolism
General aspects
Guanine - chemistry
Guanine - metabolism
Medical sciences
Molecular Sequence Data
Pharmacology. Drug treatments
Polymerase Chain Reaction
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Summary:The 2-amino group of guanine is believed to be a critical determinant of potential DNA binding sites for echinomycin and related quinoxaline antibiotics. In order to probe its importance directly we have studied the interaction between echinomycin and DNA species in which guanine N(2) is deleted by virtue of substitution of inosine for guanosine residues. The polymerase chain reaction was used to prepare inosine-substituted DNA. Binding of echinomycin, assessed by DNAase I footprinting, was practically abolished by incorporation of inosine into one or both strands of DNA. We conclude that both the purines in the preferred CpG binding site need to bear a 2-amino group to interact with echinomycin.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/20.21.5601