title: Binding of actinomycin D to DNA: evidence for a nonclassical high-affinity binding mode that does not require GpC sites.
abstract: We have employed a combination of temperature-dependent UV absorption spectroscopy, circular dichroism, and batch calorimetry to characterize the binding of actinomycin D to a series of oligomeric DNA duplexes. We find the duplex [d(CGTCGACG)]2 to be unique in its ability to bind actinomycin D strongly despite the absence of a classic GpC site. We present evidence that this non-GpC-containing duplex binds two actinomycin D molecules in an apparently cooperative manner to form a complex that exhibits aberrant spectroscopic and calorimetric behavior. We propose that these observations are consistent with actinomycin D exhibiting a high-affinity, sequence-dependent DNA-binding mode distinct from its classic binding to isolated GpC sites.
authors.affiliation: University Chemical Laboratory, Cambridge, United Kingdom.
authors.forename: J G
authors.initials: JG
authors.lastname: Snyder
authors.forename: N G
authors.initials: NG
authors.lastname: Hartman
authors.forename: B L
authors.initials: BL
authors.lastname: D'Estantoit
authors.forename: O
authors.initials: O
authors.lastname: Kennard
authors.forename: D P
authors.initials: DP
authors.lastname: Remeta
authors.forename: K J
authors.initials: KJ
authors.lastname: Breslauer
mesh_terms: D001483:Base Sequence; D002151:Calorimetry; D002942:Circular Dichroism; D004247:DNA; D003609:Dactinomycin; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D009838:Oligodeoxyribonucleotides; D003609:Dactinomycin; D004247:DNA