3 years ago

A small-molecule acts as a ‘roadblock’ on DNA, hampering its fundamental processes

A small-molecule acts as a ‘roadblock’ on DNA, hampering its fundamental processes
DNA replication, RNA and protein synthesis are the most fundamental housekeeping processes involved in an organism's growth. Failure or dysregulation of these pathways are often deleterious to life. Therefore, selective inhibition of such processes can be crucial for the inhibition of the growth of any cell, including cancer cells, pathogenic bacteria or other deadly microbes. In the present study, a Zn2+ complex is shown to act as a roadblock of DNA. The Zn2+ complex inhibited DNA taq polymerase activity under the in vitro conditions of PCR. Under in vivo conditions, it readily crosses the cell wall of gram-negative bacteria (E. coli), leading to the reduction of RNA levels as well as protein content. Growth of pathogenic bacteria (e.g., Staphylococcus aureus and Pseudomonas aeruginosa) was also significantly retarded. The Zn2+ complex binds to the grooves of the DNA without inducing conformational changes or exhibiting chemical nuclease activity. To the best current knowledge, this is first coordination complex exhibiting a ‘roadblock’ property under both in vitro and in vivo conditions (show at all three levels – DNA, RNA and protein). The label-free approach used in this study may offer an alternative route towards fighting pathogenic bacteria or cancer cells by hampering fundamental cellular processes.

Publisher URL: www.sciencedirect.com/science

DOI: S0162013417303665

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