EXOCYCLIC DNA ADDUCTS--SYNTHETIC AND ANALYTIC STUDIES
EXOCYCLIC DNA ADDUCTS--SYNTHETIC AND ANALYTIC STUDIES
批准号:
6416841
负责人:
FRANCIS JOHNSON
金额:
$11.52万
依托单位国家:
美国
项目类别:
财政年份:
2001
资助国家:
美国
项目状态:
已结题
起止时间:
2001-02-01 至 2002-01-31
关键词:
DNA damage DNA repair acrolein adduct analytical chemistry carmustine crosslink deoxyadenosines enzyme mechanism glycosylation lipid peroxides nucleic acid chemical synthesis nucleoside analog nucleosides oligonucleotides protective chemical group synthetic nucleic acid synthetic nucleotide vinyledene chloride
中文摘要
描述:(申请人描述)本部分描述的有机化学、合成化学和分析化学旨在支持相关项目中的生物和物理化学研究。主要目标是为合成DNA低聚物提供以其dmt -磷酰胺形式衍生的修饰的2'-脱氧核苷(必要时n保护)。修饰的核苷包括三组:(a)代表或模拟由亲电试剂或活性氧化物质引起的DNA损伤的核苷,(b)用于DNA修复酶研究的正常天然底物的不可水解模拟物,以及激活后形成外环加合物或链间交联的核苷。两大主题主导着合成化学。第一种方法是在核苷侧链上有一个邻乙二醇,通过高碘酸氧化可以转化为醛。后者将在合成后产生所需的内收碱基。用这种方法可以原位合成与芳烃醛、巴豆醛、脂质过氧化加合物、天然碱基和核糖内酯有关的加合物。这种方法也会产生交叉链接。第二个主题涉及使用“碳”嘌呤和嘧啶作为正常碱基和氧化或内合形式的内源性DNA损伤的稳定或不可水解的模拟物。这些将用于:(a)涉及DNA修复酶(如MutY)运作机制的研究,包括外翻(翻转)过程,(b)用于诱变机制的研究,以及(c)获得DNA修复酶复合物的晶体结构。
英文摘要
DESCRIPTION: (Applicant's Description) The organic, synthetic, and analytical chemistry described in this section of the program is designed to support biological and physico-chemical studies in the accompanying projects. The primary goal is to provide modified 2'-deoxynucleosides derivatized in the form of their DMT-phosphoramidites (N-protected where necessary) for synthetic DNA oligomers. The modified nucleosides comprise three groups: (a) those that represent or mimic damage induced in DNA by electrophiles or by reactive oxidizing species, (b) those that are non-hydrolysable mimics of the normal natural substrates for studies of DNA repair enzymes, and those that after activation will form exocyclic adducts or inter-strand crosslinks. Two main themes dominate the synthetic chemistry. The first involves having a vicinal glycol in a nucleoside side-chain that by periodate oxidation can be converted to an aldehyde. The latter will generate the desired adducted base, post-synthetically. Adducts related to araldehyde, crotonaldehyde, lipid peroxidation adducts, the natural abasic site, and ribonolactone will be synthesized in situ by this method. Cross-links also will be generated by this approach. The second theme concerns the use of "carba" purines and pyrimidines as stable or non-hydrolysable mimics of both normal bases and oxidized or adducted forms of endogenous DNA damage. These will be used: (a) in studies involving mechanisms by which DNA repair enzymes such as MutY operate, including the eversion (flip-out) process, (b) for studies of mutagenic mechanisms, and (c) to obtain crystal structures of complexes with DNA repair enzymes.
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PROJECT 1- CHEMICAL BIOLOGY OF ARISTOLOCHIC ACIDS
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批准号:8069935
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项目类别:
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资助金额:$46.87万
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财政年份:2010
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依托单位:
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批准号:7305791
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SYNTHESIS & STRUCTURE OF OLIGODEOXYNUCLEOTIDES WITH DEFINED DNA DAMAGE
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批准号:6575676
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项目类别:
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资助金额:$21.9万
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财政年份:2002
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负责人:FRANCIS JOHNSON
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依托单位:
EXOCYCLIC DNA ADDUCTS--SYNTHETIC AND ANALYTIC STUDIES
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批准号:6563822
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项目类别:
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资助金额:$11.52万
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财政年份:2002
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负责人:FRANCIS JOHNSON
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依托单位:
SYNTHESIS & STRUCTURE OF OLIGODEOXYNUCLEOTIDES WITH DEFINED DNA DAMAGE
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批准号:6443871
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项目类别:
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资助金额:$21.9万
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财政年份:2001
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负责人:FRANCIS JOHNSON
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依托单位:
SYNTHESIS & STRUCTURE OF OLIGODEOXYNUCLEOTIDES WITH DEFINED DNA DAMAGE
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批准号:6301314
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项目类别:
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资助金额:$21.9万
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财政年份:2000
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负责人:FRANCIS JOHNSON
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依托单位:
SYNTHESIS & STRUCTURE OF OLIGODEOXYNUCLEOTIDES WITH DEFINED DNA DAMAGE
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批准号:6352909
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项目类别:
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资助金额:$21.9万
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财政年份:2000
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负责人:FRANCIS JOHNSON
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依托单位:
EXOCYCLIC DNA ADDUCTS--SYNTHETIC AND ANALYTIC STUDIES
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批准号:6300325
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项目类别:
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资助金额:$20.69万
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财政年份:2000
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负责人:FRANCIS JOHNSON
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依托单位:
EXOCYCLIC DNA ADDUCTS--SYNTHETIC AND ANALYTIC STUDIES
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批准号:6102494
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项目类别:
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资助金额:$20.69万
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财政年份:1999
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批准号:6106123
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资助金额:$19.84万
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财政年份:1999
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EXOCYCLIC ADDUCTS--SYNTHETIC AND ANALYTIC STUDIES
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批准号:6269370
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项目类别:
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资助金额:$19.17万
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财政年份:1998
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负责人:FRANCIS JOHNSON
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依托单位:
SYNTHESIS OF OLIGODEOXYNUCLEOTIDES BEARING MUTAGENS AS SITE-SPECIFIED ADDUCTS
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批准号:6271015
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项目类别:
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资助金额:$19.07万
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财政年份:1998
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负责人:FRANCIS JOHNSON
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依托单位:
EXOCYCLIC ADDUCTS--SYNTHETIC AND ANALYTIC STUDIES
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批准号:6237006
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项目类别:
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资助金额:$19.69万
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财政年份:1997
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负责人:FRANCIS JOHNSON
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依托单位:
SYNTHESIS OF OLIGODEOXYNUCLEOTIDES BEARING MUTAGENS AS SITE-SPECIFIED ADDUCTS
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批准号:6239429
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项目类别:
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资助金额:$18.06万
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财政年份:1997
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负责人:FRANCIS JOHNSON
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TOTAL SYNTHESIS OF THE ANTIBIOTIC THERMORUBIN
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批准号:3129079
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项目类别:
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资助金额:$8.61万
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财政年份:1983
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负责人:FRANCIS JOHNSON
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依托单位:
EXOCYCLIC ADDUCTS--SYNTHETIC AND ANALYTIC STUDIES
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批准号:5207516
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:FRANCIS JOHNSON
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依托单位:--
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批准号:8274431
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项目类别:
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资助金额:$39.07万
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财政年份:--
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负责人:FRANCIS JOHNSON
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依托单位:
PROJECT 1- CHEMICAL BIOLOGY OF ARISTOLOCHIC ACIDS
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批准号:7837662
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项目类别:
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资助金额:$43.94万
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财政年份:--
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SYNTHESIS OF POTENTIAL INHIBITORS OF HIV REVERSE TRANSCRIPTASE
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资助金额:$0.0万
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财政年份:--
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负责人:FRANCIS JOHNSON
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SYNTHESIS OF POTENTIAL INHIBITORS OF HIV REVERSE TRANSCRIPTASE
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批准号:3814768
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:FRANCIS JOHNSON
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海外基金