Morphological effects of G-quadruplex stabilization using a small molecule in zebrafish

Agarwal, Tani ; Lalwani, Mukesh Kumar ; Kumar, Santosh ; Roy, Saumya ; Chakraborty, Tushar Kanti ; Sivasubbu, Sridhar ; Maiti, Souvik (2014) Morphological effects of G-quadruplex stabilization using a small molecule in zebrafish Biochemistry, 53 (7). pp. 1117-1124. ISSN 0006-2960

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Zebrafish (Danio rerio) embryos are transparent and advantageous for studying early developmental changes due to ex utero development, making them an appropriate model for studying gene expression changes as a result of molecular targeting. Zebrafish embryos were injected with a previously reported G-quadruplex selective ligand, and the phenotypic changes were recorded. We report marked discrepancies in the development of intersegmental vessels. In silico analysis determined that the putative G-quadruplex motif occur in the upstream promoter region of the Cdh5 (N-cadherin) gene. A real-time polymerase chain reaction-based investigation indicated that in zebrafish, CDH-2 (ZN-cad) was significantly downregulated in the ligand-treated embryos. Biophysical characterization of the interaction of the ligand with the G-quadruplex motif found in this promoter yielded strong binding and stabilization of the G-quadruplex with this ligand. Hence, we report for the first time the phenotypic impact of G-quadruplex targeting with a ligand in a vertebrate organism. This study has unveiled not only G-quadruplex targeting in non-human animal species but also the potential that G-quadruplexes can provide a ready tool for understanding the phenotypic effects of targeting certain important genes involved in differentiation and developmental processes in a living eukaryotic organism.

Item Type:Article
Source:Copyright of this article belongs to American Chemical Society.
ID Code:103377
Deposited On:02 Feb 2018 03:47
Last Modified:02 Feb 2018 03:47

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