Double-strand DNA hydrolysis by dilanthanide complexes.
Although there has been progress in developing artificial hydrolytic DNA cleaving agents, none of these has been shown to carry out the double-strand hydrolysis of DNA. We demonstrate that La(III) or Ce(IV) combined with the ligand 1,3-diamino-2-hydroxypropane-N,N,N', N'-tetraacetate (HPTA) in a 2 : 1 ratio can efficiently cleave supercoiled plasmid DNA at 55 degrees C within a 3-h period. Analysis of end-labeled restriction fragments cleaved by these complexes reveals 3'- and 5'-ends consistent with a hydrolytic mechanism. Unlike for other polydentate carboxylate complexes, plasmid DNA cleavage by La(2)(HPTA) or Ce(2)(HPTA) affords a significant amount of linear DNA with a considerable fraction of the supercoiled form still remaining. This result implies that La(2)(HPTA) and Ce(2)(HPTA) can carry out double-strand cleavage of plasmid DNA. La(2)(HPTA) and Ce(2)(HPTA) represent the first metal complexes demonstrated to be capable of double-strand hydrolytic cleavage of plasmid DNA.
Branum
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ME
Department of Chemistry and Center for Metals in Biocatalysis University of Minnesota, 207 Pleasant Street S.E., Minneapolis MN 55455, USA.
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D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004278:DNA, Superhelical / Q000187:drug effects / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D006868:Hydrolysis; D008674:Metals, Rare Earth / Q000494:pharmacology*; D010957:Plasmids / Q000235:genetics
D004278:DNA, Superhelical; D008674:Metals, Rare Earth; D004247:DNA