INVESTIGATION OF DNA CLEAVING 1,3 DIOXO 1,2 DITHIOLANES
INVESTIGATION OF DNA CLEAVING 1,3 DIOXO 1,2 DITHIOLANES
批准号:
6118504
负责人:
Kent S Gates
金额:
$0.02万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1998
资助国家:
美国
项目状态:
已结题
起止时间:
1998-08-01 至 1999-07-31
中文摘要
这项研究的目的是阐明这种机制
英文摘要
The research is designed to elucidate the mechanism by which
1,3-dioxo-1,2-dithiolanes related to anti-tumor antibiotic leinamycin
(1) cleave deoxyribonucleic acid (DNA). In vitro experiments showed
that DNA-cleavage by LM is triggered by added thiol, but does not
involve radicals. Importantly, it was found that S-deoxyleinamycin
(2) displays no biological activity and does not cleave DNA in in
vitro experiments. Thus, it appears that the unusual
1,3-dioxo-1,2-dithiolane ring (3) is required for DNA-cleavage by LM.
At this time, the chemical mechanism of DNA cleavage by LM is
completely unknown and no detailed proposals for this chemistry have
been made. In our preliminary work, we have identified simple,
synthetic 1,3-dioxo-1,2-dithiolanes that, like leinamycin, cleave DNA
in a thiol-dependent manner. The work we describe herein has three
main goals: we will (1) investigate the structural requirements for
DNA cleavage by dioxodithiolanes, (2) determine the chemical mechanism
by which dioxodithiolanes cleave DNA, (3) design and synthesize novel
thiol-triggered DNA-cleaving agents that utilize the dioxodithiolane
"core." In order to meet these goals, we will synthesize a series of
analogs in which we systematically alter the functionality on the
dioxodithiolane ring system. We will produce evidence for (or
against) our proposed mechanism by studying the reactivity of these
analogs with DNA and in chemical model reactions. We plan to apply
the information that we gain regarding the cleavage of DNA by
dioxodithiolanes toward the design of novel DNA-cleaving agents that
combine this DNA-cleaving functional group with a DNA-binding moiety
of know affinity and specificity .
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会议论文
Cross-links at abasic sites in duplex DNA
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批准号:10524017
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项目类别:
-
资助金额:$39.47万
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财政年份:2012
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负责人:Kent S Gates
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依托单位:
Cross-links At Abasic Sites in Duplex DNA
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批准号:8664848
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项目类别:
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资助金额:$31.6万
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财政年份:2012
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负责人:Kent S Gates
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依托单位:
Cross-links At Abasic Sites in Duplex DNA
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批准号:8867233
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项目类别:
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资助金额:$32.16万
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财政年份:2012
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负责人:Kent S Gates
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依托单位:
Cross-links At Abasic Sites in Duplex DNA
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批准号:8372731
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项目类别:
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资助金额:$33.04万
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财政年份:2012
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负责人:Kent S Gates
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依托单位:
Cross-links at abasic sites in duplex DNA
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批准号:10295786
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项目类别:
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资助金额:$39.63万
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财政年份:2012
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负责人:Kent S Gates
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依托单位:
Cross-links at abasic sites in duplex DNA
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批准号:10054954
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项目类别:
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资助金额:$39.78万
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财政年份:2012
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负责人:Kent S Gates
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依托单位:
Cross-links At Abasic Sites in Duplex DNA
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批准号:8531243
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项目类别:
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资助金额:$31.29万
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财政年份:2012
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负责人:Kent S Gates
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依托单位:
Chemical and Biological Mechanisms of Leinamycin
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批准号:7028123
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项目类别:
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资助金额:$27.88万
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财政年份:2006
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负责人:Kent S Gates
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依托单位:
Chemical and Biological Mechanisms of Leinamycin
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批准号:7286021
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项目类别:
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资助金额:$25.87万
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财政年份:2006
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负责人:Kent S Gates
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依托单位:
Conference Grant: "DNA Alkylation: From Natural Products to Chemotherapy"
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批准号:7159973
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项目类别:
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资助金额:$0.5万
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财政年份:2006
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负责人:Kent S Gates
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依托单位:
Chemical and Biological Mechanisms of Leinamycin
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批准号:7470547
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项目类别:
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资助金额:$25.87万
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财政年份:2006
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负责人:Kent S Gates
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依托单位:
Chemical and Biological Mechanisms of Leinamycin
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批准号:7663837
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项目类别:
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资助金额:$25.87万
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财政年份:2006
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负责人:Kent S Gates
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依托单位:
Chemical and Biological Mechanisms of Leinamycin
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批准号:7900900
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项目类别:
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资助金额:$25.87万
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财政年份:2006
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负责人:Kent S Gates
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依托单位:
DNA Damage by Tumor Cell-Specific N-Oxides
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批准号:6858673
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项目类别:
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资助金额:$17.03万
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财政年份:2003
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负责人:Kent S Gates
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依托单位:
DNA Damage by Tumor Cell-Specific N-Oxides
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批准号:6602990
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项目类别:
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资助金额:$17.04万
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财政年份:2003
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负责人:Kent S Gates
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依托单位:
DNA Damage by Tumor Cell-Specific N-Oxides
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批准号:6717697
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项目类别:
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资助金额:$17.03万
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财政年份:2003
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负责人:Kent S Gates
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依托单位:
DNA Damage by Tumor Cell-Specific N-Oxides
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批准号:7016287
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项目类别:
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资助金额:$16.62万
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财政年份:2003
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负责人:Kent S Gates
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依托单位:
DNA ALKYLATION BY THE ANTITUMOR ANTIBIOTIC LEINAMYCIN
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批准号:6031193
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项目类别:
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资助金额:$15.7万
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财政年份:1999
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负责人:Kent S Gates
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依托单位:
DNA Alkylation by Leinamycin
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批准号:6989438
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项目类别:
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资助金额:$18.96万
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财政年份:1999
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负责人:Kent S Gates
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依托单位:
DNA Alkylation by Leinamycin
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批准号:7424973
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项目类别:
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资助金额:$17.98万
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财政年份:1999
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负责人:Kent S Gates
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依托单位:
海外基金