Jump to main content
Jump to site search

Issue 34, 2017, Issue in Progress
Previous Article Next Article

Restriction of telomerase capping by short non-toxic peptides via arresting telomeric G-quadruplex

Author affiliations

Abstract

The stabilization of a G-quadruplex structure in human telomeric DNA has become a promising strategy in the development of cancer therapeutics. Here, we report FK13 (a small fragment of human cathelicidin peptide LL37, residues 17–29) and its mutant peptides (KR12A, KR12B and KR12C) inhibiting telomerase activity by stabilizing the telomeric G-quadruplex structures. An array of biophysical studies like fluorescence anisotropy, circular dichroism spectroscopy, circular dichroism melting, isothermal titration calorimetry, and high resolution nuclear magnetic resonance spectroscopy, in conjunction with molecular dynamics simulations, are employed to examine the interaction of peptides with the G-quadruplex structure. Furthermore, the peptide-quadruplex interaction is monitored in ex vivo systems, the telomerase over-expressed MCF7 breast adeno-carcinoma cell line. MTT assay and flow cytometry studies indicate selective antiproliferative activities of the peptides towards cancer cells over normal kidney epithelial cell line. Confocal microscopy evidenced nuclear transport and localisation of the peptides. A telomerase repeat amplification protocol assay further evidences telomere uncapping and abrogation of telomerase catalysing activity upon administration of peptides. Hence, arresting G-quadruplex structures using short peptides brings in a new mechanistic insight for the development of future peptide based therapeutics against cancer.

Graphical abstract: Restriction of telomerase capping by short non-toxic peptides via arresting telomeric G-quadruplex

Back to tab navigation

Supplementary files

Article information


Submitted
13 Dec 2016
Accepted
23 Mar 2017
First published
12 Apr 2017

This article is Open Access

RSC Adv., 2017,7, 20888-20899
Article type
Paper

Restriction of telomerase capping by short non-toxic peptides via arresting telomeric G-quadruplex

J. Jana, P. Sengupta, S. Mondal and S. Chatterjee, RSC Adv., 2017, 7, 20888
DOI: 10.1039/C6RA28149D

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

Reproduced material should be attributed as follows:

  • For reproduction of material from NJC:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
  • For reproduction of material from PCCP:
    [Original citation] - Published by the PCCP Owner Societies.
  • For reproduction of material from PPS:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
  • For reproduction of material from all other RSC journals:
    [Original citation] - Published by The Royal Society of Chemistry.

Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.


Social activity

Search articles by author

Spotlight

Advertisements