Platinum binding preferences dominate the binding of novel polyamide amidine anthraquinone platinum(ii) complexes to DNA

被引:2
|
作者
Lo, Anthony T. S. [1 ]
Chen, Jon K. [2 ]
Murray, Vincent [2 ]
Todd, Matthew H. [1 ,3 ]
Hambley, Trevor W. [1 ]
机构
[1] Univ Sydney, Sch Chem, Camperdown, NSW 2006, Australia
[2] Univ New South Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia
[3] UCL, UCL Sch Pharm, 29-39 Brunswick Sq, London WC1N 1AX, England
关键词
SEQUENCE SPECIFICITY; SUPERCOILED DNA; CROSS-LINKS; DAMAGE; CISPLATIN; AGENT; SELECTIVITY; DRUGS;
D O I
10.1039/d1dt03539h
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
Complexes incorporating a threading anthraquinone intercalator with pyrrole lexitropsin and platinum(ii) moieties attached were developed with the goal of generating novel DNA binding modes, including the targeting of AT-rich regions in order to have high cytotoxicities. The binding of the complexes to DNA has been investigated and profiles surprisingly similar to that for cisplatin were observed; the profiles were different to those for a complex lacking the pyrrole lexitropsin component. The lack of selective binding to AT-rich regions suggests the platinum binding was dominating the sequence selectivity, and is consistent with the pyrrole lexitropsin slowing intercalation. The DNA unwinding profiles following platinum binding were evaluated by gel electrophoresis and suggested that intercalation and platinum binding were both occurring.
引用
收藏
页码:17945 / 17952
页数:8
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