Kinetically favored platination of adenine in the G-rich human telomeric repeat

Lu Rao, Ulrich Bierbach

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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 (t1/2 = 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.

Original languageEnglish (US)
Pages (from-to)15764-15765
Number of pages2
JournalJournal of the American Chemical Society
Volume129
Issue number51
DOIs
StatePublished - Dec 26 2007
Externally publishedYes

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Adenine
Platinum
DNA
G-Quadruplexes
Intercalating Agents
Acridines
Telomere
High performance liquid chromatography
Antineoplastic Agents
Cisplatin
Mass spectrometry
Assays
Mass Spectrometry
High Pressure Liquid Chromatography
Technology
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Kinetically favored platination of adenine in the G-rich human telomeric repeat. / Rao, Lu; Bierbach, Ulrich.

In: Journal of the American Chemical Society, Vol. 129, No. 51, 26.12.2007, p. 15764-15765.

Research output: Contribution to journalArticle

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