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

Lu Rao; Ulrich Bierbach

doi:10.1021/ja077390a

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

Lu Rao, Ulrich Bierbach

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

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 (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.

Original language	English (US)
Pages (from-to)	15764-15765
Number of pages	2
Journal	Journal of the American Chemical Society
Volume	129
Issue number	51
DOIs	https://doi.org/10.1021/ja077390a
State	Published - Dec 26 2007
Externally published	Yes

ASJC Scopus subject areas

Catalysis
Chemistry(all)
Biochemistry
Colloid and Surface Chemistry

Access to Document

10.1021/ja077390a

Cite this

@article{65861176023041abacd76494a28d1ef5,

title = "Kinetically favored platination of adenine in the G-rich human telomeric repeat",

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.",

author = "Lu Rao and Ulrich Bierbach",

year = "2007",

month = dec,

day = "26",

doi = "10.1021/ja077390a",

language = "English (US)",

volume = "129",

pages = "15764--15765",

journal = "Journal of the American Chemical Society",

issn = "0002-7863",

publisher = "American Chemical Society",

number = "51",

}

TY - JOUR

T1 - Kinetically favored platination of adenine in the G-rich human telomeric repeat

AU - Rao, Lu

AU - Bierbach, Ulrich

PY - 2007/12/26

Y1 - 2007/12/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=37549050199&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=37549050199&partnerID=8YFLogxK

U2 - 10.1021/ja077390a

DO - 10.1021/ja077390a

M3 - Article

C2 - 18047349

AN - SCOPUS:37549050199

SN - 0002-7863

VL - 129

SP - 15764

EP - 15765

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 51

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this