title: Double-strand hydrolysis of DNA by a magnesium(II) complex with diethylenetriamine.
abstract: The development of artificial nucleases that hydrolyze DNA or RNA is of great interest in molecular biology, biotechnology, and medicine. We now report that a magnesium(II) complex of diethylenetriamine (Mg-dien) can effectively promote the double-stranded cleavage of plasmid DNA and the dideoxynucleotide dApdA under physiological conditions of pH and temperature. Experiments performed in the presence of hydrogen peroxide, radical scavengers, or under rigorously anaerobic conditions indicate that DNA cleavage mediated by Mg-dien occurs via a hydrolytic path. Mg-dien efficiently hydrolyzes supercoiled pBR322 DNA and the pseudo-first-order rate constant at 37 degrees C and pH 8.0 is estimated to be 1.60 h(-1). The dinucleotide dApdA hydrolysis, with Mg-dien at 170 microM, shows a rate enhancement factor of ca. 5 x 10(8). 1H and 31P(1H) NMR studies show that Mg-dien effectively hydrolyzes 5'-dAMP to give deoxyadenosine and inorganic phosphate. While Mg2+ has been found at the catalytic sites of many natural nucleases, Mg-dien appears to be the first synthetic Mg2+-containing system capable of hydrolyzing dideoxynucleotides and DNA and thus may provide a simple model system to assist mechanistic studies of naturally occurring nucleases.
authors.affiliation: Institute of Molecular Science, Shanxi University, 030006 Taiyuan, Shanxi Province, China. yangpin@sxu.edu.cn
authors.forename: Pin
authors.initials: P
authors.lastname: Yang
authors.forename: Rui
authors.initials: R
authors.lastname: Ren
authors.forename: Maolin
authors.initials: M
authors.lastname: Guo
authors.forename: Aixin
authors.initials: A
authors.lastname: Song
authors.forename: Xiangli
authors.initials: X
authors.lastname: Meng
authors.forename: Caixia
authors.initials: C
authors.lastname: Yuan
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhou
authors.forename: Huili
authors.initials: H
authors.lastname: Chen
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Xiong
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Gao
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D003851:Deoxyribonucleases / Q000737:chemistry*; D015226:Dinucleoside Phosphates; D006868:Hydrolysis; D008274:Magnesium / Q000737:chemistry*; D018716:Molecular Mimicry; D015394:Molecular Structure; D010957:Plasmids; D011073:Polyamines / Q000737:chemistry*
chemical_list: D015226:Dinucleoside Phosphates; D011073:Polyamines; C005391:diethylenetriamine; D004247:DNA; D003851:Deoxyribonucleases; D008274:Magnesium