Thiazole orange-carboplatin triplex-forming oligonucleotide (TFO) combination probes enhance targeted DNA crosslinking

Joseph Hennessy; Piotr Klimkowski; Daniel Singleton; Alex Gibney; Malou Coche; Nicholas P. Farrell; Afaf H. El-Sagheer; Tom Brown; Andrew Kellett

doi:10.1039/D3MD00548H

Thiazole orange-carboplatin triplex-forming oligonucleotide (TFO) combination probes enhance targeted DNA crosslinking†

Joseph Hennessy,

^a Piotr Klimkowski,^b Daniel Singleton,^c Alex Gibney,

^a Malou Coche,^a Nicholas P. Farrell,

^d Afaf H. El-Sagheer,^bef Tom Brown

^b and Andrew Kellett

*^a

Author affiliations

* Corresponding authors

^a SSPC, The Science Foundation Ireland Research Centre for Pharmaceuticals, School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland
E-mail: andrew.kellett@dcu.ie

^b Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, UK

^c ATDBio Ltd., School of Chemistry, University of Southampton, Southampton, UK

^d Department of Chemistry, Virginia Commonwealth University, Richmond, VA 23284-2006, USA

^e School of Chemistry, University of Southampton, Southampton, UK

^f Department of Science and Mathematics, Faculty of Petroleum and Mining, Engineering, Suez University, Suez 43721, Egypt

Abstract

We report a new class of carboplatin-TFO hybrid that incorporates a bifunctional alkyne–amine nucleobase monomer called AP-C3-dT that enables dual ‘click’ platinum(II) drug conjugation and thiazole orange fluorophore coupling. Thiazole orange enhances the binding of Pt(II)-TFO hybrids and provides an intrinsic method for monitoring triplex formation. These hybrid constructs possess increased stabilisation and crosslinking properties in comparison to earlier Pt(II)-TFOs, and demonstrate sequence-specific binding at neutral pH.

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DOI: https://doi.org/10.1039/D3MD00548H
Article type: Research Article
Submitted: 03 Oct 2023
Accepted: 27 Oct 2023
First published: 31 Oct 2023
This article is Open Access

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RSC Med. Chem., 2024,15, 485-491

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Thiazole orange-carboplatin triplex-forming oligonucleotide (TFO) combination probes enhance targeted DNA crosslinking

J. Hennessy, P. Klimkowski, D. Singleton, A. Gibney, M. Coche, N. P. Farrell, A. H. El-Sagheer, T. Brown and A. Kellett, RSC Med. Chem., 2024, 15, 485 DOI: 10.1039/D3MD00548H

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

RSC Medicinal Chemistry

Thiazole orange-carboplatin triplex-forming oligonucleotide (TFO) combination probes enhance targeted DNA crosslinking†

Abstract

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Thiazole orange-carboplatin triplex-forming oligonucleotide (TFO) combination probes enhance targeted DNA crosslinking

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