Selective recognition of c-MYC G-quadruplex DNA using prolinamide derivatives

Chauhan, Ajay ; Paladhi, Sushovan ; Debnath, Manish ; Dash, Jyotirmayee (2016) Selective recognition of c-MYC G-quadruplex DNA using prolinamide derivatives Organic and Biomolecular Chemistry, 14 (24). pp. 5761-5767. ISSN 1477-0520

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Official URL: http://doi.org/10.1039/C6OB00177G

Related URL: http://dx.doi.org/10.1039/C6OB00177G

Abstract

Herein we report the design, synthesis, biophysical and biological evaluation of triazole containing prolinamide derivatives as selective c-MYC G-quadruplex binding ligands. A modular synthetic route has been devised for prolinamide derivatives using a copper(I) catalyzed azide–alkyne cycloaddition (CuAAC). The Förster resonance energy transfer (FRET) melting assay indicates that prolinamide trimers can significantly stabilize G-quadruplex structures over duplex DNA compared to prolinamide dimers. The fluorescent intercalator displacement (FID) assay shows that a trimer with prolinamide side chains at the para-position of the benzene ring can discriminate between different quadruplex structures and exhibits the highest binding affinity towards the c-MYC G-quadruplex structure. Molecular modeling studies reveal that the prolinamide trimer stacks upon the terminal G-quartet of the c-MYC G-quadruplex. Atomic force microscopy (AFM) analysis reveals that the tris-prolinamide ligand can be used to regulate the assembly of novel supramolecular nanoarchitectures. Further, in vitro cellular studies with human hepatocellular carcinoma (HepG2) cells indicate that the tris-prolinamide derivatives can inhibit cell proliferation and reduce c-MYC expression in cancer cells.

Item Type:Article
Source:Copyright of this article belongs to Royal Society of Chemistry.
ID Code:126589
Deposited On:17 Oct 2022 05:47
Last Modified:17 Oct 2022 05:47

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