INOR 606 |
| Mimicking the activities of nucleases is currently an attractive research area in molecular biology since artificial nucleases have potential applications as novel restriction enzymes and anticancer therapeutic agents. In most recent work, effort has focused on di- or polynuclear metal complexes, which are typically more reactive than the corresponding mononuclear metal complexes. Nevertheless, their activity is still much lower than that of the corresponding enzymes. In nature, the high reactivity of nucleases is attributed to the cooperation of the prothetic metal irons with several functional groups of the amino acid side chains present in the active site. The positively charged residues of lysine, arginine and histidine are thought to stabilize phosphorane-like transition states by electronstatic interactions, hydrogen bonding and/or proton transfer. Applying this function, several examples of synthetic systems have been reported and exhibited the dramatically enhanced activity by introducing hydrogen bonding donors to bimetallic complexes. 2,6-bis[((2-hydroxybenzyl)(2-pyridylmethyl)amino)methyl]-4-methylphenol (La), which provides a N4O3-donor coordination sphere, has been reported as the model ligand of phosphatase. Based on La, we recently prepared two novel dinucleating ligands Lb and Lc with bisammonium and bisguanidinium groups, respectively. Their metalations were carried out through incubating ligands with 2-equiv FeCl3°¤6H2O in H2O/CH3OH (50:50), and diiron complexes Fe2La, Fe2Lb and Fe2Lc were accordingly obtained and characterized by ESI-MS. After incubation of DNA in the presence of 50 uM of Fe2La at pH 7.0 and 37 oC for 1 h, only about 67% of form I have been nicked. However, for Fe2Lb and Fe2Lc, just 10 uM were required to convert completely from the supercoiled form I to the nicked form II and eventually to the linearized form III. This indicates a much more pronounced DNA cleavage efficiency for the introducing of bisammonium and bisguanidinium groups.
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Inorganic Modeling of Biological Systems
7:00 PM-10:00 PM, Tuesday, August 21, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Inorganic Chemistry |
