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
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
收藏
页码:485 / 491
页数:8
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