Morphological Effects of G-Quadruplex Stabilization Using a Small Molecule in Zebrafish

Agarwal, Tani and Lalwani, Mukesh Kumar and Kumar, Santosh and Roy, Saumya and Chakraborty, Tushar Kanti and Sivasubbu, Sridhar and Maiti, Souvik (2014) Morphological Effects of G-Quadruplex Stabilization Using a Small Molecule in Zebrafish. In: BIOCHEMISTRY, 53 (7). pp. 1117-1124.

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Abstract

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:	Journal Article
Publication:	BIOCHEMISTRY
Publisher:	AMER CHEMICAL SOC
Additional Information:	Copyright for this article belongs to the AMER CHEMICAL SOC, USA
Department/Centre:	Division of Chemical Sciences > Organic Chemistry
Date Deposited:	15 Apr 2014 06:30
Last Modified:	15 Apr 2014 06:30
URI:	http://eprints.iisc.ac.in/id/eprint/48856

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