DNA Adducts of Lipid Peroxidation Products
脂质过氧化产物的 DNA 加合物
基本信息
- 批准号:6685891
- 负责人:
- 金额:$ 26.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-03-01 至 2006-11-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION: (PROVIDED BY APPLICANT) The covalent modification of DNA is
believed to be the initial step in chemical carcinogenesis. Exposure to
carcinogens is often a result of environmental or work conditions, diet or
smoking. Recently, considerable attention has been focused on genotoxins that
are formed endogenously as a result of oxidative stress. Exposure to these
compounds is unavoidable. There is emerging evidence that constituents of
cigarette smoke stimulate oxidative stress, resulting in elevated levels of
lipid peroxidation products. The peroxidation of lipids gives a complex array
of electrophilic species. A number of relatively simple unsaturated aldehydes
(2-enals) have been identified and shown to react with DNA bases to form
hydroxypropano adducts. These enals can also undergo further oxidation to
2,3-epoxyaldehydes which react with DNA to give etheno adducts. The
epoxyaldehydes have been shown to be more potent genotoxins than the parent
enals. The long-term goal of this program is to develop strategies for the
site-specific synthesis of oligonucleotides in which nucleobases have been
modified by lipid peroxidation products to form complex etheno adducts. The
modification of the nucleobase often generates new stereogenic centers, which
will be controlled by our synthetic approaches. Thus, our aim is to not only to
synthesize site-specifically modified oligonucleotides, but stereochemically
defined adducts as well. During the course of our studies, enantioselective
syntheses of the lipid peroxidation products will also be achieved.
Collaborations have been established to examine the structure and biology of
the mutagens. Structural studies will be performed using multi-dimensional NMR
methods. In combination with mutagenesis experiments, we hope to establish
structure-activity relationships of these mutagenic lesions. A collaboration to
examine the detoxification of the various stereoisomers of lipid peroxidation
products with epoxide hydrolase and glutathione transferase will also be
pursued.
说明:(由申请人提供)DNA的共价修饰是
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Carmelo J Rizzo其他文献
Carmelo J Rizzo的其他文献
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{{ truncateString('Carmelo J Rizzo', 18)}}的其他基金
Project 1: Synthetic Approaches to Carcinogen-Linked Oxyoligonucleotides
项目 1:致癌物相关含氧寡核苷酸的合成方法
- 批准号:
8119100 - 财政年份:2010
- 资助金额:
$ 26.43万 - 项目类别:
Synthesis, StructUre and Replication of Carcirogen-Modified Oligonucleotides
致癌物修饰寡核苷酸的合成、结构和复制
- 批准号:
8369307 - 财政年份:2009
- 资助金额:
$ 26.43万 - 项目类别:
Synthesis, StructUre and Replication of Carcirogen-Modified Oligonucleotides
致癌物修饰寡核苷酸的合成、结构和复制
- 批准号:
7781467 - 财政年份:2009
- 资助金额:
$ 26.43万 - 项目类别:
Synthesis, StructUre and Replication of Carcirogen-Modified Oligonucleotides
致癌物修饰寡核苷酸的合成、结构和复制
- 批准号:
8002022 - 财政年份:2009
- 资助金额:
$ 26.43万 - 项目类别:
Synthesis, StructUre and Replication of Carcirogen-Modified Oligonucleotides
致癌物修饰寡核苷酸的合成、结构和复制
- 批准号:
8196770 - 财政年份:2009
- 资助金额:
$ 26.43万 - 项目类别:
Project 1: Synthetic Approaches to Carcinogen-Linked Oxyoligonucleotides
项目 1:致癌物相关含氧寡核苷酸的合成方法
- 批准号:
7208780 - 财政年份:2006
- 资助金额:
$ 26.43万 - 项目类别:
ACQUISITION OF A 500 MHZ LC-NMR:DNA CARCINOGEN CHEMISTRY
获取 500 MHZ LC-NMR:DNA 致癌化学物质
- 批准号:
7166160 - 财政年份:2005
- 资助金额:
$ 26.43万 - 项目类别:
ACQUISITION OF A 500 MHZ LC-NMR: PEPTIDE CHEMISTRY
采集 500 MHZ LC-NMR:肽化学
- 批准号:
7166161 - 财政年份:2005
- 资助金额:
$ 26.43万 - 项目类别:
ACQUISITION OF A 500 MHZ LC-NMR: NEUROPHARMACOLOGY
采集 500 MHZ LC-NMR:神经药理学
- 批准号:
7166162 - 财政年份:2005
- 资助金额:
$ 26.43万 - 项目类别:
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