Selective recognition of consecutive G sequence in double-stranded DNA by a zinc(II)-macrocyclic tetraamine complex appended with an anthraquinone.
A zinc (II) complex with a macrocyclic tetraamine appended with an anthraquinone ((9,10-anthraquinon-2-yl)methyl-1,4,7,10-tetraazacyclododecane, ZnL, anthraquinonyl-cyclen) selectively recognizes consecutive G sequence in double-stranded DNA. The affinity of the Zn2+-anthraquinonyl-cyclen to consecutive dG groups in DNA was disclosed by comparison of K(app) values (=[DNA-bound ZnL]/[uncomplexed ZnL][uncomplexed nucleobase in DNA]) determined by the UV spectrophotometric titrations at pH 8, I=0.1 (NaNO3), and 25 degrees C for poly(dG) x poly(dC) (K(app) = 1.5 x 10(5) M(-1)), poly(dG-dC)2 (2.8 x 10(4) M(-1)), poly(dA-dT)2 (4.3 x 10(4) M(-1)), and calf thymus DNA (2.8 x 10(4) M(-1)). The corresponding K(app) values with the Zn2+-free ligand were 5.3 x 10(3) M(-1), 7.4 x 10(3) M(-1), 7.4 x 10(3) M(-1), and 5.9 x 10(3) M(-1), respectively. The selective recognition of consecutive G sequence was concluded from the DNase I footprinting of SV40 early promotor DNA fraction (197 bp) containing a TATA box and six GC boxes. The present finding is in remarkable contrast to the previous selective T-recognition by Zn2+-cyclen complexes appended with acridine, quinoline(s), and naphthalene(s) [J. Am. Chem. Soc. 121 (1999) 5426]. While the Zn2+-acridinyl-cyclen inhibited TATA binding protein from interacting with a TATA box consensus DNA [J. Inorg. Biochem. 79 (2000) 253], the present Zn2+-anthraquinonyl-cyclen inhibited the Sp1 transcriptional factor protein from interacting with a GC box-consensus DNA.
Kikuta
E
E
Department of Medicinal Chemistry, Faculty of Medicine, Hiroshima University, Japan.
Matsubara
R
R
Katsube
N
N
Koike
T
T
Kimura
E
E
D000880:Anthraquinones / Q000737:chemistry* / Q000378:metabolism; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D018983:DNA Footprinting; D004996:Ethidium / Q000737:chemistry; D006147:Guanine / Q000032:analysis* / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry* / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D013053:Spectrophotometry; D015032:Zinc / Q000737:chemistry*
D000880:Anthraquinones; D009942:Organometallic Compounds; D006147:Guanine; D004247:DNA; D004996:Ethidium; D015032:Zinc