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RATIONAL DEVELOPMENT OF NOVEL ANTIAIDS DRUGS

新型抗艾滋病药物的合理开发

基本信息

批准号：
2672063
负责人：
SYLVIA LEE-HUANG
金额：
$ 25.04万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-01-01 至 2000-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2672063
关键词：
AIDS DNA topoisomerases N glycosidase antiAIDS agent drug design /synthesis /production enzyme inhibitors human immunodeficiency virus 1 integrase molecular cloning plant proteins protein purification protein structure function site directed mutagenesis tissue /cell culture

项目摘要

DESCRIPTION: (Adapted from Applicant's Abstract) The long term objective of this application is to further develop two lead compounds, MAP 30 and GAP 31, which have shown three activities that may be critical to the antiviral action. These include RNA N-glycosidase, DNA topoinactivation,and HIV-integrase which are critical target in selective antiviral therapy. In the revised application Dr. Lee-Huang proposes to study the followings: Peptide fragmentation and activity mapping of MAP 30 and GAP 31 to define the domains responsible for anti-HIV activity, ribosome inactivation, DNA tipoinactivation and HIV-integrase inhibition; recombinant expression and site-specific mutagenesis to facilitate rational development of effective anti-HIV mimetic. The identification of domains responsible for these activities of MAP 30 and GAP 31 will be important in: revealing the requirements for the structure and function of these proteins; defining the extent to which these activities, or whether in all of them, contribute to the anti-HIV action; and identifying particular peptide sequences or fragment that confer anti-HIV activity. This may provide ideal therapeutic tools for the treatment of AIDS. Such defined peptides may be conveniently synthesized and easily modulated for improved efficiency. Many AIDS organizations and AIDS patient groups have expressed strong support of her work. This work may provides insight into the mechanism underlying the antiviral activity of these compounds, and will hopefully contribute to the development of clinically useful drugs.

描述：（改编自申请人的摘要）本申请是进一步开发两种先导化合物MAP 30和GAP 31，已经显示出三种可能对抗病毒药物至关重要的活性，行动上这些包括RNA N-糖苷酶，DNA拓扑异构酶活化，整合酶是选择性抗病毒治疗的关键靶点。在修订后的应用程序博士李-黄建议研究以下内容： MAP 30和GAP 31的肽片段化和活性图谱，以确定负责抗HIV活性、核糖体失活、DNA tipoin活化和HIV整合酶抑制;重组表达和位点特异性诱变，以促进合理开发有效抗HIV模拟物。确定负责这些的域活动的MAP 30和GAP 31将是重要的：揭示这些蛋白质的结构和功能的要求;定义这些活动或所有这些活动在多大程度上有助于抗HIV作用;以及鉴定特定的肽序列或赋予抗HIV活性片段。这可能提供理想的治疗治疗艾滋病的工具。此类定义的肽可以方便地合成和易于调制以提高效率。许多艾滋病艾滋病组织和艾滋病患者团体表示强烈支持她工作这项工作可能提供了深入了解的机制，这些化合物的抗病毒活性，并有望有助于开发临床上有用的药物。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Anti-HIV plant proteins catalyze topological changes of DNA into inactive forms.

抗 HIV 植物蛋白催化 DNA 拓扑变化为非活性形式。

DOI：
发表时间：
1992
期刊：
BioFactors (Oxford, England)
影响因子：
0
作者：
Huang,PL;Chen,HC;Kung,HF;Huang,PL;Huang,P;Huang,HI;Lee-Huang,S
通讯作者：
Lee-Huang,S

Transcriptional activation by artificial recruitment in mammalian cells.

哺乳动物细胞中人工募集的转录激活。

DOI：
10.1073/pnas.96.6.2674
发表时间：
1999
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Nevado,J;Gaudreau,L;Adam,M;Ptashne,M
通讯作者：
Ptashne,M

Live-cell real-time imaging of mitochondria in HIV-1-infected cells.

HIV-1 感染细胞中线粒体的活细胞实时成像。