PURINE METABOLISM IN SCHISTOSOMA MANSONI
曼索尼血吸虫的嘌呤代谢
基本信息
- 批准号:3566967
- 负责人:
- 金额:$ 15.79万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1986
- 资助国家:美国
- 起止时间:1986-08-01 至 1992-07-31
- 项目状态:已结题
- 来源:
- 关键词:Escherichia coli RNA splicing Schistosoma mansoni X ray crystallography anthelmintics complementary DNA computer graphics /printing drug design /synthesis /production enzyme inhibitors enzyme mechanism enzyme structure gene expression genetic library genetic manipulation genetic mapping hypoxanthine phosphoribosyltransferase laboratory mouse molecular cloning nucleic acid repetitive sequence parasitic disease chemotherapy peptide chemical synthesis plasmids protein sequence purine /pyrimidine metabolism restriction mapping schistosomiasis tubercidin
项目摘要
One of the potential benefits of comparative biochemical studies of
parasites is the identification of metabolic deficiencies in the latter and
the exploitation of these vulnerabilities for antiparasitic chemotherapy.
We have recently verified the absence of de novo synthesis of purine
nucleotides in Schistosoma mansoni and proceeded to delineate the purine
salvage pathways in this organism. Our results pointed to
hypoxanthine-guanine phosphoribosyl transferase (HGPRT) as one of the
pivotal enzymes in the purine salvage by S. mansoni; an effective
inhibition of this enzyme would lead to death of the parasite. We have
since purified this enzyme to apparent homogeneity, partially characterized
it and found many of its properties differ from those of the mammalian
HGPRT; thus raising the possibility of selective inhibition of the parasite
HGPRT. Our future research plan calls for; (1) searching for specific and
potent inhibitors of S. mansoni HGPRT and pursuing their possible use as
antischistosomal agents; (2) cloning the c-DNA encoding S. mansoni HGPRT
and comparing its restriction map and nucleotide sequences with the known
amino acid sequence of mammalian HGPRT for possible differences in protein
structures between the two enzymes; (3) cloning the full-length c-DNA of S.
mansoni HGPRT. This will be done either by introducing a specially
constructed expression vector plasmid into an Escherichia coli #165 strain
deleted in xanthine-guanine phosphoribosyl transferase (XGPRT) for
expression; or by introducing a c-DNA library of S. mansoni constructed in
retroviral LTR chimeric plasmids into a mammalian HGPRT cell line and
selecting for the expression of S. mansoni HGPRT in HAT medium. The native
S. mansoni HGPRT thus produced in larger quantities by these methods will
facilitate more thorough investigations on the kinetic and structural of
the enzyme; (4) cloning the genomic DNA encoding S. mansoni HGPRT and
comparing its full size, restriction pattern and nucleotide sequences with
the full-length S. mansoni HGPRT c-DNA to search for possible introns in
the gene structure and any regulatory segments flanking the gene in order
to better understand the genetic regulation of S. mansoni HGPRT. We have
also identified a tubercidin kinase in S. mansoni which has a unique
substrate specificity and is the target of the potent antischistosomal
activity of tubercidin. We plan to further characterize this enzyme as a
potential target for antischistosomal chemotherapy.
比较生物化学研究的一个潜在好处是,
寄生虫是后者代谢缺陷的鉴定,
利用这些弱点进行抗寄生虫化疗。
我们最近证实了没有从头合成嘌呤
曼氏血吸虫的核苷酸,并继续描绘嘌呤
在这个有机体中的补救途径。 我们的研究结果表明,
次黄嘌呤-鸟嘌呤磷酸核糖转移酶(HGPRT)作为一种
关键酶的嘌呤补救的S。有效的
这种酶的抑制将导致寄生虫的死亡。 我们有
由于将该酶纯化至表观均一性,
发现它的许多特性与哺乳动物的不同
从而提高了选择性抑制寄生虫的可能性
HGPRT。 我们未来的研究计划要求:(1)寻找特定的,
S. mansoni HGPRT,并寻求其可能的用途,
(2)克隆编码S.曼索尼HGPRT
并将其限制性酶切图谱和核苷酸序列与已知的
哺乳动物HGPRT的氨基酸序列,用于蛋白质中可能的差异
(3)克隆了S.
mansoni HGPRT。 这将通过引入一个专门的
将构建的表达载体质粒导入大肠杆菌#165菌株
黄嘌呤-鸟嘌呤磷酸核糖转移酶(XGPRT)缺失,
表达;或通过引入S.曼索尼建于
将逆转录病毒LTR嵌合质粒导入哺乳动物HGPRT细胞系,
选择表达S. mansoni HGPRT在HAT培养基中培养。 天然
S.因此,通过这些方法大量生产的mansoni HGPRT将
促进对动力学和结构的更彻底的调查,
(4)克隆编码S. mansoni HGPRT和
将其全长、限制性酶切图谱和核苷酸序列与
全长S. mansoni HGPRT c-DNA来寻找可能的内含子,
基因结构和基因侧翼的任何调控片段,
为了更好地了解S. mansoni HGPRT。 我们有
还在S. mansoni有一个独特的
底物特异性,是强效抗组胺药的靶点。
杀结核菌素的活性。 我们计划进一步将这种酶定性为
潜在的靶点。
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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Ching Chung WANG其他文献
Ching Chung WANG的其他文献
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{{ truncateString('Ching Chung WANG', 18)}}的其他基金
CLINICAL TRIAL: PEDIATRIC STUDY OF SODIUM PHENYLBUTYRATE W/TYPE II/III SPINAL MU
临床试验:II 型/III 型脊髓 MU 苯丁酸钠的儿科研究
- 批准号:
7717950 - 财政年份:2007
- 资助金额:
$ 15.79万 - 项目类别:
CHARACTERIZATION & IDENTIFICATION OF 20S PROTEASOME SUBUNITS
特征描述
- 批准号:
6308854 - 财政年份:2000
- 资助金额:
$ 15.79万 - 项目类别:
CHARACTERIZATION & IDENTIFICATION OF 20S PROTEASOME SUBUNITS
特征描述
- 批准号:
6120256 - 财政年份:1999
- 资助金额:
$ 15.79万 - 项目类别:
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