Jump to main content
Jump to site search

Issue 24, 2016
Previous Article Next Article

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

Author affiliations

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.

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

  • This article is part of the themed collection: New Talent
Back to tab navigation

Supplementary files

Article information


Submitted
21 Jan 2016
Accepted
03 Mar 2016
First published
10 Mar 2016

Org. Biomol. Chem., 2016,14, 5761-5767
Article type
Paper

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

A. Chauhan, S. Paladhi, M. Debnath and J. Dash, Org. Biomol. Chem., 2016, 14, 5761
DOI: 10.1039/C6OB00177G

Social activity

Search articles by author

Spotlight

Advertisements