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

被引：2

作者：

Hennessy, Joseph ^{[1
]}

Klimkowski, Piotr ^{[2
]}

Singleton, Daniel ^{[3
]}

Gibney, Alex ^{[1
]}

Coche, Malou ^{[1
]}

Farrell, Nicholas P. ^{[4
]}

El-Sagheer, Afaf H. ^{[2
,5
,6
]}

Brown, Tom ^{[2
]}

Kellett, Andrew ^{[1
]}

机构：

[1] Dublin City Univ, Sci Fdn Ireland Res Ctr Pharmaceut, Sch Chem Sci, SSPC, Dublin, Ireland

[2] Univ Oxford, Chem Res Lab, 12 Mansfield Rd, Oxford OX1 3TA, England

[3] Univ Southampton, Sch Chem, ATDBio Ltd, Southampton SO17 1BJ, England

[4] Virginia Commonwealth Univ, Dept Chem, Richmond, VA 23284 USA

[5] Univ Southampton, Sch Chem, Southampton SO17 1BJ, England

[6] Suez Univ, Fac Petr & Min, Dept Sci & Math, Engn, Suez 43721, Egypt

来源：

RSC MEDICINAL CHEMISTRY | 2024年 / 15卷 / 02期

基金：

欧盟地平线“2020”; 爱尔兰科学基金会; 英国生物技术与生命科学研究理事会;

关键词：

GENE; RECOGNITION; SURROGATE;

D O I：

10.1039/d3md00548h

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. 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.

引用

页码：485 / 491

页数：8

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