DIDEMNINS--SYNTHETIC STUDIES AND MECHANISM OF ACTION
DIDEMNINS--SYNTHETIC STUDIES AND MECHANISM OF ACTION
批准号:
2683442
负责人:
MADELEINE M JOULLIE
金额:
$24.94万
依托单位国家:
美国
项目类别:
财政年份:
1985
资助国家:
美国
项目状态:
已结题
起止时间:
1985-09-30 至 2000-03-31
关键词:
X ray crystallography affinity chromatography affinity labeling antineoplastics antiviral agents biological products circular dichroism conformation cyclic peptides drug design /synthesis /production drug receptors immunosuppressive molecular dynamics oligopeptides peptide analog peptide chemical synthesis photochemistry protein structure function receptor binding stereochemistry
中文摘要
地德明是具有免疫抑制、抗病毒和抗肿瘤活性的环缩酚肽。
和抗肿瘤活性。 最有效的同源物具有特殊的
抗增殖效力(IC 50 = 1- 10 nM),具有完整的细胞活力。 的
生物活性的机制基础仍然是
不确定;然而,据信,didemnins发挥其作用,
通过与其他免疫抑制剂不同的机制,
药物如环孢菌素A、FK-506或雷帕霉素。
该项目旨在研究和澄清结构和机制
生物学特性的基础上。 主要目标是
具有系统结构新颖的地德明类似物的合成
修改. 这些类似物的测试将允许进一步的
建立构效关系(SAR)谱。 的
第二个目标是全合成didemnin同系物,
最近报道。 这些新化合物的合成路线将允许
进行生物学测试和探索其药用潜力
剂. 第三个目标是制备供研究用的合成地德明
外部合作者。 这些调查将集中在
生物活性的地德明类似物的构象研究,
衍生物,以及didemnins和受体之间的相互作用
proteins.
总之,这项研究旨在研究生物学
活性的didemnin环缩酚酸肽通过一个程序,
化学合成和生物学评价。 在结构和
机制问题围绕有效的抗增殖和抗肿瘤
didemnins的活动已经澄清,将有可能
更彻底地评估这个天然家族的药用潜力
产品.
英文摘要
The didemnins are cyclic depsipeptides having immunosuppressive, antiviral
and antitumor activities. The most potent congeners have exceptional
antiproliferative potency (IC50 = 1-10nM) with intact cell viability. The
mechanistic basis of the biological activities of didemnins is still
uncertain; however, it is believed that didemnins exert their effects
through a mechanism which is distinct from that of other immunosuppressive
agents such as cyclosporin A, FK-506 or rapamycin.
This project seeks to study and clarify the structural and mechanistic
basis of the biological properties of the didemnins. The primary goal is
the synthesis of novel didemnin analogs containing systematic structural
modifications. Testing of these analogs will allow for the further
development of a structure-activity relationship (SAR) profile. The
second goal is the total synthesis of didemnin congeners which have been
recently reported. Synthetic routes to these novel compounds will allow
for biological testing and exploration of their potential as medicinal
agents. The third goal is the preparation of synthetic didemnin for study
by outside collaborators. These investigations will focus on
conformational studies of biologically active didemnin analogs and
derivatives, as well as interactions between didemnins and receptor
proteins.
In conclusion, this research is designed to investigate the biological
activities of the didemnin cyclic depsipeptides through a program of
chemical synthesis and biological evaluation. After the structural and
mechanistic issues surround the potent antiproliferative and antitumor
activities of didemnins have been clarified, it will be possible to
evaluate more thoroughly the medicinal potential of this family of natural
products.
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Didemnins and Ustiloxins as Probes of Cell Proliferation
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批准号:7845468
-
项目类别:
-
资助金额:$1.28万
-
财政年份:2009
-
负责人:MADELEINE M JOULLIE
-
依托单位:
DIDEMNINS AND USTILOXINS AS PROBES OF CELL PROLIFERATION
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批准号:6512349
-
项目类别:
-
资助金额:$31.57万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
SYNTHESIS OF BIOLOGICALLY ACTIVE CYCLODEPSIPEPTIDES
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批准号:2090102
-
项目类别:
-
资助金额:$22.5万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
DIDEMNINS--SYNTHETIC STUDIES AND MECHANISM OF ACTION
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批准号:2894635
-
项目类别:
-
资助金额:$25.9万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
SYNTHESIS AND CONFORMATIONAL STUDIES OF DIDEMNINS A, B
-
批准号:3179571
-
项目类别:
-
资助金额:$10.69万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
SYNTHESIS AND CONFORMATIONAL STUDIES OF DIDEMNINS A, B
-
批准号:3179572
-
项目类别:
-
资助金额:$10.97万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
Didemnins and Ustiloxins as Probes of Cell Proliferation
-
批准号:7385154
-
项目类别:
-
资助金额:$31.68万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
DIDEMNINS--SYNTHETIC STUDIES AND MECHANISM OF ACTION
-
批准号:2873319
-
项目类别:
-
资助金额:$2.83万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
SYNTHESIS OF BIOLOGICALLY ACTIVE CYCLODEPSIPEPTIDES
-
批准号:3179573
-
项目类别:
-
资助金额:$21.77万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
DIDEMNINS--SYNTHETIC STUDIES AND MECHANISM OF ACTION
-
批准号:6038364
-
项目类别:
-
资助金额:$3.77万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
DIDEMNINS--SYNTHETIC STUDIES AND MECHANISM OF ACTION
-
批准号:2390663
-
项目类别:
-
资助金额:$23.93万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
SYNTHESIS OF BIOLOGICALLY ACTIVE CYCLODEPSIPEPTIDES
-
批准号:3179570
-
项目类别:
-
资助金额:$20.53万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
SYNTHESIS AND CONFORMATIONAL STUDIES OF DIDEMNINS A, B
-
批准号:3179567
-
项目类别:
-
资助金额:$9.05万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
Didemnins and Ustiloxins as Probes of Cell Proliferation
-
批准号:7082009
-
项目类别:
-
资助金额:$32.64万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
SYNTHESIS OF BIOLOGICALLY ACTIVE CYCLODEPSIPEPTIDES
-
批准号:3179574
-
项目类别:
-
资助金额:$22.06万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
DIDEMNINS--SYNTHETIC STUDIES AND MECHANISM OF ACTION
-
批准号:2090105
-
项目类别:
-
资助金额:$23.19万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
Didemnins and Ustiloxins as Probes of Cell Proliferation
-
批准号:6983956
-
项目类别:
-
资助金额:$33.43万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
SYNTHESIS AND CONFORMATIONAL STUDIES OF DIDEMNINS A, B (
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批准号:3179565
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项目类别:
-
资助金额:$10.8万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
DIDEMNINS AND USTILOXINS AS PROBES OF CELL PROLIFERATION
-
批准号:6375728
-
项目类别:
-
资助金额:$30.79万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
Didemnins and Ustiloxins as Probes of Cell Proliferation
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批准号:7225209
-
项目类别:
-
资助金额:$31.69万
-
财政年份:1985
-
负责人:MADELEINE M JOULLIE
-
依托单位:
海外基金