title: Binding of actinomycin C1 (D) and actinomin to base-modified oligonucleotide duplexes with parallel chain orientation.
abstract: The binding of actinomycin D (C1, 1) and its analog actinomin (2) was studied on base-modified oligonucleotide duplexes with parallel chain orientation (ps) and with anti-parallel chains (aps) for comparison. Actinomycin D binds not only to aps duplexes containing guanine-cytosine base pairs but also to those incorporating modified bases such as 7-deazaguanine or its 6-deoxo derivative. For this, novel phosphoramidites were prepared. The new building block of 7-deaza-2'-deoxyguanosine is significantly more stable than the one currently used and allows normal oxidation conditions during solid-phase oligonucleotide synthesis. Actinomycin binds weakly to ps duplexes containing guanine-isocytosine base pairs but not to ps-DNA incorporating pairs of isoguanine-cytosine residues. On the contrary, the actinomycin D analog actinomin, which contains positively charged side chains instead of the chiral peptide rings, is strongly bound to both ps- and aps-DNA. Guanines, isoguanine, as well as other 7-deaza derivatives are accepted as nucleobases. Apparently, the pentapeptide lacton rings of actinomycin do not fit nicely into the groove of ps-DNA thereby reducing the binding strength of the antibiotic while the groove size of ps-DNA does not affect actinomin binding notably.
authors.affiliation: Laboratorium für Organische und Bioorganische Chemie, Institut für Chemie, Universität Osnabrück, Barbarastrasse 7, 49069 Osnabrück, Germany.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Peng
authors.forename: Peter
authors.initials: P
authors.lastname: Leonard
authors.forename: Frank
authors.initials: F
authors.lastname: Seela
mesh_terms: D001665:Binding Sites; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry; D003609:Dactinomycin / Q000031:analogs & derivatives* / Q000737:chemistry*; D006860:Hydrogen Bonding; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry; D010084:Oxidation-Reduction; D012680:Sensitivity and Specificity; D013696:Temperature
chemical_list: D009841:Oligonucleotides; D009943:Organophosphorus Compounds; C434331:phosphoramidite; D003609:Dactinomycin; C010007:actinomine; D004247:DNA