Issue 103, 2016, Issue in Progress

Doxorubicin binds to duplex RNA with higher affinity than ctDNA and favours the isothermal denaturation of triplex RNA

Abstract

The interaction of doxorubicin (DOX) with triplex, duplex and single RNA helices has been studied by fluorimetric, circular dichroism, viscometry, DSC, ITC, T-jump kinetic relaxation technique and fluorescence lifetime measurements in near physiological conditions (pH = 7, I = 0.1 M and 25 °C). DOX binds to the groove of poly(rA)·2poly(rU), while it intercalates into poly(rA)·poly(rU) and forms external complex with poly(rA) and poly(rU). Fluorescence lifetime measurements have shown that all the RNA/DOX complexes are non-fluorescent. The affinity with the duplex is some 15 times greater than with the triplex; this behaviour favours the isothermal denaturation of the triplex/DOX complex according to reaction poly(rA)·2poly(rU)/DOX + DOX ⇌ poly(rA)·poly(rU)/DOX + poly(rU)/DOX, that is, the reaction shifts to right upon increasing the DOX content. ITC measurements have revealed that, under the same conditions, the affinity of DOX with the RNA duplex is higher than with ctDNA, a striking outcome as long as the binding of DOX to DNA seems to be the origin of its biological action.

Graphical abstract: Doxorubicin binds to duplex RNA with higher affinity than ctDNA and favours the isothermal denaturation of triplex RNA

Article information

Article type
Paper
Submitted
25 Aug 2016
Accepted
17 Oct 2016
First published
17 Oct 2016

RSC Adv., 2016,6, 101142-101152

Doxorubicin binds to duplex RNA with higher affinity than ctDNA and favours the isothermal denaturation of triplex RNA

A. R. Rubio, N. Busto, J. M. Leal and B. García, RSC Adv., 2016, 6, 101142 DOI: 10.1039/C6RA21387A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements