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Research Article

Short designed peptide unfolding human telomeric G-quadruplex: mimicking the helicase function

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Pages 9977-9986 | Received 06 Sep 2022, Accepted 16 Nov 2022, Published online: 28 Nov 2022
 

Abstract

Human telomeric DNA can fold into G-quadruplex structures involving the interaction of four guanine bases in a square planar arrangement. The highly distinctive nature of quadruplex topologies suggests that they can act as novel therapeutic targets. In this study, we provide the evidence of human telomeric G4 destabilization in dilute and cell-mimicking molecular crowing conditions upon peptide binding. We have used three human telomeric sequences of different lengths. CD data showed that these sequences folded into anti-parallel G-quadruplex and CD intensity decreased significantly on increasing the peptide concentration. UV-thermal melting results showed significant decrease in hypochromicity due to formation of G4-peptide complex at 295 nm. Fluorescence data showed the quenching on titrating the peptide with human telomere G4. Electrophoretic mobility shift assay confirmed the unfolding of G4 structure. Cell viability was significantly reduced in the presence of QW5 peptide with IC50 values as 8.78 μM and 7.72 μM after 72 and 96 hours of incubation respectively. These results confirmed that QW5 peptide has an ability to bind and unfold to human telomeric G-quadruplex and hence might be the key modulator for targeting diseases having over-representation of G4 motifs and their destabilization will be helpful in increasing the efficiency of DNA replication, transcription or duplex reannealing.

Communicated by Ramaswamy H. Sarma

Acknowledgements

The timely help from Prof. Shrikant Kukreti and Dr. Anju Singh of Nucleic Acid Research Laboratory, Delhi University.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

We thank ‘Department of Biotechnology (DBT)’, Govt of India for research funding to this project (SAN No. 102/IFD/SAN/864/2018-2019).

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