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DNA sequence preferences for the anti‐cancer drug mitoxanthrone and related anthraquinones revealed by DNase I footprinting
Author(s) -
Fox K.R.,
Waring M.J.,
Brown J.R.,
Neidle S.
Publication year - 1986
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(86)80703-7
Subject(s) - anthraquinones , footprinting , dna , dna footprinting , chemistry , mitoxantrone , deoxyribonuclease i , anthraquinone , sequence (biology) , base pair , biochemistry , stereochemistry , biology , microbiology and biotechnology , gene , genetics , base sequence , dna binding protein , transcription factor , botany , organic chemistry , chemotherapy
The interaction has been studied of several anthraquinone‐based intercalating drugs, including the anti‐cancer agent mitoxantrone, with defined sites of DNA. A 160 base pair DNA sequence from tyrT was employed for footprinting with DNase I. The anthraquinones had aminoalkylamino substituents in various positions of the ring system. Inhibition of enzymatic cutting of the DNA was observed at various positions on the sequence, mostly around some of the pyrimidine‐3',5'‐purine sites. Enhancements to cutting were observed clustered around AT‐rich regions. The compounds showed differences in detailed footprinting behaviour, which have been related to differences in their mode of interaction with DNA as found in earlier computer modelling studies.