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

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.

SUBMITTER: Hennessy J

PROVIDER: S-EPMC10880910 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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

Hennessy Joseph J Klimkowski Piotr P Singleton Daniel D Gibney Alex A Coche Malou M Farrell Nicholas P NP El-Sagheer Afaf H AH Brown Tom T Kellett Andrew A

RSC medicinal chemistry 20231031 2

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- ...[more]

PMID: 38389892

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