Binding of actinomycin C-1 (D) and actinomin to base-modified oligonucleotide duplexes with parallel chain orientation

Autor(en): Li, Hong
Peng, Xiaohua
Leonard, Peter
Seela, Frank
Stichwörter: 7-DEAZA-2'-DEOXYISOGUANOSINE; actinomin; actinomycin D; base-modified nucleotides; binding; Biochemistry & Molecular Biology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; COMPLEX; CRYSTAL-STRUCTURE; DERIVATIVES; FLUORESCENCE; ISOGUANINE; MISMATCHES; parallel DNA; Pharmacology & Pharmacy; SPECIFICITIES; STRANDED-DNA; TETRANUCLEOTIDE SEQUENCES
Erscheinungsdatum: 2006
Herausgeber: PERGAMON-ELSEVIER SCIENCE LTD
Journal: BIOORGANIC & MEDICINAL CHEMISTRY
Volumen: 14
Ausgabe: 12
Startseite: 4089
Seitenende: 4100
Zusammenfassung: 
The binding of actinomycin D (Cl, 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'-deoxyguano sine 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. (c) 2006 Elsevier Ltd. All rights reserved.
ISSN: 09680896
DOI: 10.1016/j.bmc.2006.02.002

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