Structural elucidation of a novel DNA-DNA cross-link of 1,2,3,4-diepoxybutane.

Structural elucidation of a novel DNA-DNA cross-link of 1,2,3,4-diepoxybutane. Research Abstract Details 

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Structural elucidation of a novel DNA-DNA cross-link of 1,2,3,4-diepoxybutane. Abstract Text:

Natalia Tretyakova,Alina Livshits,Soobong Park,Bimi Bisht,Melissa Goggin,

DNA-DNA cross-linking by 1,2,3,4-diepoxybutane (DEB) is considered the molecular basis for its potent cytotoxic and genotoxic effects. DEB reactions with DNA initially lead to N7-(2'-hydroxy-3',4'-epoxybut-1'-yl)-guanine monoadducts, which can then alkylate neighboring DNA bases to form bifunctional lesions. We recently reported the structures of four regioisomeric guanine-adenine adducts of DEB involving the N7 position of guanine and the N1, N3, N6, and N7 positions of adenine (Park, S., et al. (2004) Chemical Research in Toxicology 17, 1638-1651). In the present work, a novel bifunctional DNA lesion of DEB was identified as 1-(hypoxanth-1-yl)-4-(guan-7-yl)-2,3-butanediol (N1HX-N7G-BD). An authentic standard of N1HX-N7G-BD was prepared and structurally characterized by proton NMR, UV, and mass spectrometry. HPLC-ESI-MS/MS analyses of acid hydrolysates of DEB-treated calf thymus DNA revealed a peak that had the same retention time, MS/MS fragmentation, and UV spectrum as the authentic standard of N1HX-N7G-BD. We propose that N1HX-N7G-BD is formed by the hydrolytic deamination of previously reported 1-(aden-1-yl)-4-(guan-7-yl)-2,3-butanediol. Although N1HX-N7G-BD adducts are less abundant in DEB-treated DNA than the corresponding guanine-guanine cross-links, they may play a role in the induction of both AT and GC base pair mutations.

Structural elucidation of a novel DNA-DNA cross-link of 1,2,3,4-diepoxybutane. Publishing Authors By Initials

N Tretyakova,A Livshits,S Park,B Bisht,M Goggin,

For similar investigative techniques: chemistry, analytical: mass spectrometry: tandem mass spectrometry research abstracts see: investigative techniques: chemistry, analytical: mass spectrometry: tandem mass spectrometry research

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Structural elucidation of a novel DNA-DNA cross-link of 1,2,3,4-diepoxybutane. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Chemical research in toxicology

VOLUME: 20

Page Numbers: 284-9

Journal Abbreviation: Chem. Res. Toxicol.

ISSN: 0893-228X

DAY: 3

MONTH: Feb

YEAR: 2007

Structural elucidation of a novel DNA-DNA cross-link of 1,2,3,4-diepoxybutane. Information

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LANGUAGE: eng

NlmUniqueID: 8807448

Structural elucidation of a novel DNA-DNA cross-link of 1,2,3,4-diepoxybutane. Keywords Mesh Terms:

KEYWORDS: Tandem Mass Spectrometry

MESH TERMS: methods

Chemical & Substance for Abstract: Structural elucidation of a novel DNA-DNA cross-link of 1,2,3,4-diepoxybutane. Information

Substance Name: calf thymus DNA

Registry Number: 91080-16-9

Grant and Affiliation Information for Structural elucidation of a novel DNA-DNA cross-link of 1,2,3,4-diepoxybutane.

AFFILIATION: University of Minnesota Cancer Center and Department of Medicinal Chemistry, Minneapolis, Minnesota 55455, USA. trety@umn.edu

Country: United States

AGENCY: United States NCI

GRANT: R01 CA100670

ACRONYM: CA

MEDLINETA: Chem Res Toxicol

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