Importance of Binding Affinity for the Activity of a Metallodendritic Chemical Nuclease.

Yi-Hsuan Tang,Chai-Lin Kao,Carol Wu,Si-Ting Liou,Sodio Hsu,Hui-Ting Chen,Po-Yu Chen

doi:10.3390/pharmaceutics10040258

Abstract

A family of bis(2-pyridyl)amino-modified poly(amidoamine) dendrimer Cu complexes was prepared, and their chemical nuclease activities and binding affinity (Kb) levels for DNA plasmid were investigated. The Kb values of the G2 to G6 apodendrimers for DNA plasmid were found to be 7.4, 23, 48, 70, and 280 µM−1, respectively, using ethidium bromide (EtBr) displacement experiments. The chemical nuclease activities of the corresponding complexes were determined by gel electrophoresis, and a clear positive dendritic effect was observed. Further analysis indicated a linear correlation between the Kb values of the G2 to G5 apodendrimers and the nuclease activity of the corresponding complexes. This observation indicated the importance of substrate binding affinity for macromolecular nuclease activity. In addition, an experiment using 3′-(p-hydroxyphenyl) fluorescein suggested that hydroxyl radicals formed under the tested conditions. Subsequently performed inhibition studies indicated that the hydroxyl radical was the active species responsible for the plasmid cleavage.

Highlights

Metallodendrimers have attracted considerable interest in the past few decades because they have the advantages of organic materials while possessing the properties of metallic ions [1,2,3]
The most significant discovery of this investigation was the establishment of a correlation between the binding affinity of copper dendrimer-based nucleases and their nuclease activity
A linear correlation between Kb and chemical nuclease activity was found among the complexes tested

Summary

Introduction

Metallodendrimers have attracted considerable interest in the past few decades because they have the advantages of organic materials while possessing the properties of metallic ions [1,2,3]. Metallonucleases are metalloenzymes that contribute to the regulation of the cell cycle by participating in the editing of nucleic acids [10] In such nucleases, catalytic metallic ions have been shown to function by either of two working mechanisms: hydrolytic or oxidative cleavage. Several types of metal ions have been shown to form metallonucleases [18,19], copper ions can act as either Lewis acids or oxidizing agents in nucleases This unique character makes copper very attractive for the study of both natural and artificial nucleases [20]

Methods

Results

Conclusion