期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 129, 期 51, 页码 15764-+出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja077390a
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资金
- NCI NIH HHS [R01 CA101880, R01 CA101880-04, CA101880] Funding Source: Medline
The interactions of PT-ACRAMTU, a cytotoxic platinum-acridine conjugate, with the human telomeric G-quadruplex have been studied using in-line high-performance liquid chromatography-mass spectrometry and footprinting assays. The conjugate reacts significantly faster with quadruplex DNA (t(1/2) = 1.2 h) than with double-stranded DNA, and A-N7, and not G-N7, is the kinetically preferred target, an unprecedented reactivity feature in platinum-DNA interactions. Unlike the clinical platinum drug cisplatin, which targets the human telomeric sequence nonspecifically, the platinum-intercalator technology has the potential to produce telomere-specific anticancer agents via a mechanism that kinetically discriminates between G and A in the two DNA secondary structures.
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