Selective recognition of consecutive G sequence in double-stranded DNA by a Zinc(II)–macrocyclic tetraamine complex appended with an anthraquinone

Abstract

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 Zn 2+–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 (NaNO 3), and 25°C for poly(dG)⋅poly(dC) ( K app=1.5×10 5 M –1), poly(dG-dC) 2 (2.8×10 4 M –1), poly(dA-dT) 2 (4.3×10 4 M –1), and calf thymus DNA (2.8×10 4 M −1). The corresponding K app values with the Zn 2+-free ligand were 5.3×10 3 M −1, 7.4×10 3 M −1, 7.4×10 3 M −1, and 5.9×10 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 Zn 2+–cyclen complexes appended with acridine, quinoline(s), and naphthalene(s) [J. Am. Chem. Soc. 121 (1999) 5426]. While the Zn 2+–acridinyl-cyclen inhibited TATA binding protein from interacting with a TATA box consensus DNA [J. Inorg. Biochem. 79 (2000) 253], the present Zn 2+–anthraquinonyl-cyclen inhibited the Sp1 transcriptional factor protein from interacting with a GC box-consensus DNA.