Kumar, A (2017) A small-molecule acts as a ‘roadblock’ on DNA, hampering its fundamental processes. Journal of Inorganic Biochemistry, 176. pp. 134-139. ISSN 0162-0134
Abstract
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 polymerase chain reaction (PCR). Under in vivo conditions, it readily crosses the cell wall of gram-negative bacteria (Escherichia 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.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2017 Elsevier Inc. This is an author produced version of a paper published in Journal of Inorganic Biochemistry. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Coordination complex; DNA binding; Fluorescence spectroscopy; DNA polymerase; ESKAPE pathogens |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Structural Molecular Biology 2 (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 27 Sep 2017 10:13 |
Last Modified: | 06 Sep 2018 00:39 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.jinorgbio.2017.08.023 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:121717 |