CHEMICAL STRUCTURE--HYPOTHALAMIC NA+/K+ ATPASE INHIBITOR
CHEMICAL STRUCTURE--HYPOTHALAMIC NA+/K+ ATPASE INHIBITOR
批准号:
2029119
负责人:
Garner Tripp Haupert
金额:
$44.65万
依托单位国家:
美国
项目类别:
财政年份:
1994
资助国家:
美国
项目状态:
已结题
起止时间:
1994-04-01 至 2000-07-31
中文摘要
描述:下丘脑抑制因子(Hypothalamic inhibitory factor, HIF)被认为是一种哺乳动物
英文摘要
DESCRIPTION: Hypothalamic inhibitory factor, HIF, is felt to be a mammalian
analog of the digitalis glycosides with biologic and biochemical properties
consistent with physiologic regulation of the mammalian sodium pump in
cardiovascular, renal and nervous system tissues in vivo. Disregulation of
the inhibitor-Na,K-ATPase system has been linked to the pathogenesis of
human essential hypertension. Structural analysis of pure HIF showed it to
be an isomer, differing in the steroid moiety, of the plant glycoside,
ouabain. Recently, an ouabain-like compound (OLC) isolated from human
plasma and felt to be indistinguishable from plant ouabain has been
restudied and found to be different from ouabain but identical to HIF,
further supporting the notion that a unique molecule may specifically
regulate the human Na,K-ATPase. The simplest explanation consistent with
our spectroscopic data was that HIF differed from ouabain as a position
isomer rhamnoside. We synthesized eight of these peracylated analogs and
obtained their CD spectra. None of them showed weak CD curves (nearly zero)
which is the signature of pentanaphthoyl HIF and OLC, nor did calculated CD
spectra of remaining position isomers, with the possible exception of the C5
rhamnoside. With the likelihood of a more complex difference in the steroid
moiety, an affinity purification method was developed using a monoclonal
anti-digoxin antibody which resulted in high yields of pure HIF, making
complete structural assignment of the endogenous Na,K-ATPase inhibitor
achievable. Development of monoclonal antibodies to characterize HIF and
create a diagnostic assay is newly proposed.
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CHEMICAL STRUCTURE OF HYPOTHALAMIC NA/K ATPASE INHIBITOR
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批准号:2229582
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项目类别:
-
资助金额:$41.79万
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财政年份:1994
-
负责人:Garner Tripp Haupert
-
依托单位:
CHEMICAL STRUCTURE--HYPOTHALAMIC NA+/K+ ATPASE INHIBITOR
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批准号:6043823
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项目类别:
-
资助金额:$42.22万
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财政年份:1994
-
负责人:Garner Tripp Haupert
-
依托单位:
CHEMICAL STRUCTURE OF HYPOTHALAMIC NA/K ATPASE INHIBITOR
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批准号:2229583
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项目类别:
-
资助金额:$43.46万
-
财政年份:1994
-
负责人:Garner Tripp Haupert
-
依托单位:
CHEMICAL STRUCTURE--HYPOTHALAMIC NA+/K+ ATPASE INHIBITOR
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批准号:2750414
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项目类别:
-
资助金额:$40.99万
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财政年份:1994
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负责人:Garner Tripp Haupert
-
依托单位:
CHEMICAL STRUCTURE OF HYPOTHALAMIC NA/K ATPASE INHIBITOR
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批准号:2229581
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项目类别:
-
资助金额:$35.85万
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财政年份:1994
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负责人:Garner Tripp Haupert
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依托单位:
CHARACTERIZATION OF HYPOTHALAMIC NA+ TRANSPORT INHIBITOR
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批准号:3345504
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项目类别:
-
资助金额:$18.59万
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财政年份:1984
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负责人:Garner Tripp Haupert
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依托单位:
CHARACTERIZATION OF HYPOTHALAMIC NA+ TRANSPORT INHIBITOR
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批准号:3345505
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项目类别:
-
资助金额:$18.64万
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财政年份:1984
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负责人:Garner Tripp Haupert
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依托单位:
海外基金