Development of functional molecules capable of recognizing and cleaving the bulge structure in DNA by using an optical active dinuclear iron complex

点击翻译按钮获取中文摘要

DNA cleaving reagent is an essentical tool for the treatment of cancers and hereditary diseases. It is expected that the reagents that can cleavage specific sequence and specific structure of DNA selectively can be applied to the antitumor drugs and the artificial restriction enzymes.In my approach to develope novel optical active dinuclear iron complexes that are capable of cleaving double-strand DNA simultaneously and sequence-selectively, I prepared six dinuclear ligands, (1,8-(N-anthranylmethyl)-bis(N',N'-dipyridylmethyl-(R,R) or (S,S)-cyclohexane-1,2-diamine (R or S-ABDC), 1,3-(N-xylylmethyl)-bis(N',N'-dpyridylmethyl-(R,R) or (S,S)-cyclohexane-1,2-diamine (m-R-BDC or m-S-BDC), and 1,4-(N-xylylmethyl)-bis(N',N'-dpyridylmethyl-(R,R) or (S,S)-cyclohexane-1,2-diamine (p-R-DBC or p-S-BDC).Moreover, I investigated plasmid pUC 19 DNA cleaving activity by iron complexes, which are prepared by mixing of ligand with FeSO_4 in buffered solution in the presence of sodium ascorbate. All the iron complexes cleaved pUC 19 DNA efficiently and were found to cleave 281 base-pair DNA with a little selectivity, indicating that the dinuclear metal-chelating moiety that connected by the linker may be necessary for the sequence selectivity of DNA strand scission.