PHYSICAL CHEMISTRY OF THERAPEUTIC PLASMA PROTEINS
PHYSICAL CHEMISTRY OF THERAPEUTIC PLASMA PROTEINS
批准号:
3336613
负责人:
KENNETH C. INGHAM
金额:
$18.72万
依托单位国家:
美国
项目类别:
财政年份:
1978
资助国家:
美国
项目状态:
已结题
起止时间:
1978-01-01 至 1986-08-31
关键词:
activation product anticoagulants antiseptic sterilization antithrombin III antithrombins blood fractionation blood preservation blood proteins chemical structure function complement enzyme substrate complex fibrin fibrinogen fluorescence spectrometry heparin human tissue intermolecular interaction plasma plasmin polyethylenes protease inhibitor radiotracer solubility thermostability zymogens
中文摘要
这项建议描述了对选定的
血浆蛋白包括抗凝血酶III、氯灭活物、α2-纤溶酶
抑制剂和纤维连接蛋白,所有这些都有潜在的替代价值
遗传性或获得性缺陷患者的治疗。该计划
将加快开发新的或改进的分离和
以适合临床评估的形式保存这些蛋白质。这个
在聚乙烯存在的情况下,将评估各种蛋白质的溶解度。
乙二醇是一种惰性分级沉淀剂,正在作为一种
乙醇的替代品,用于大规模分馏。我们将想方设法
选择性地操纵特定蛋白质的溶解度,例如通过
添加它们优先与之相互作用的物质。其次,这些
我们将检查蛋白质对各种形式的稳定性。
应激,特别强调热稳定性,目标是
定义可对其进行巴氏灭菌以降低风险的条件
输血性肝炎。最后,我们建议制定一项广泛的计划
人体蛋白质-蛋白质和蛋白质-配体相互作用的研究
等离子体,重点是荧光光谱和高压的使用
液体色谱学。要调查的系统包括:(1)相互作用
在上述三种具有相关酶和酵素的蛋白酶抑制剂中,
(2)纤维连接蛋白与纤维蛋白原、胶原和肝素的相互作用;
这些蛋白质不同片段之间的相互作用。结果是
这些研究,除了澄清结构/功能关系外,还将
应用于荧光结合分析的发展及改进
基于亲和力原理的纯化方案。
英文摘要
This proposal describes research into the physicochemical properties of selected
plasma proteins including antithrombin III, Cl-inactivator, alpha2-plasmin
inhibitor, and fibronectin, all of which have potential value for replacement
therapy in patients with either inherited or acquired deficiences. The program
will expedite the development of new or improved methods of isolating and
preserving these proteins in a form suitable for clinical evaluation. The
solubility of various proteins will be evaluated in the presence of polyethylene
glycol, an inert fractional precipitating agent, which is being developed as an
alternative to ethanol for large-scale fractionation. We will seek ways of
selectively manipulating the solubility of specific proteins, for example by
addition of substances with which they preferentially interact. Secondly, these
proteins will be examined with respect to their stability towards various forms
of stress, with particular emphasis on thermal stability, the objective being to
define conditions under which they can be pasteurized to diminish the risk of
transfusion hepatitis. Finally, we propose to develop a broad program of
investigation of protein-protein and protein-ligand interactions in human
plasma, with emphasis on the use of fluorescence spectroscopy and high pressure
liquid chromatography. Systems to be investigated include: (1) the interaction
of the above three protease inhibitors with the relevant proteases and zymogens,
(2) the interaction of fibronectin with fibrin(ogen), collagen, and heparin, (3)
the interaction between various fragments of these proteins. The results of
these studies, in addition to clarifying structure/function relationships, will
be applied to the development of fluorescent binding assays and improved
purification schemes based on affinity principles.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Core--Macromolecular analysis and interactions
-
批准号:6644330
-
项目类别:
-
资助金额:$13.59万
-
财政年份:2002
-
负责人:KENNETH C. INGHAM
-
依托单位:
SHARED CIRCULAR DICHROMETER/FLUOROMETER
-
批准号:6291973
-
项目类别:
-
资助金额:$11.0万
-
财政年份:2001
-
负责人:KENNETH C. INGHAM
-
依托单位:
Core--Macromolecular analysis and interactions
-
批准号:6504144
-
项目类别:
-
资助金额:$13.59万
-
财政年份:1996
-
负责人:KENNETH C. INGHAM
-
依托单位:
DOMAIN STRUCTURE OF PLATELET INTEGRIN IIB-IIIA
-
批准号:3432702
-
项目类别:
-
资助金额:$2.0万
-
财政年份:1993
-
负责人:KENNETH C. INGHAM
-
依托单位:
DOMAIN STRUCTURE OF PLATELET INTEGRIN IIB-IIIA
-
批准号:2291749
-
项目类别:
-
资助金额:$2.0万
-
财政年份:1993
-
负责人:KENNETH C. INGHAM
-
依托单位:
DOMAIN STRUCTURE OF PLATELET INTEGRIN IIB-IIIA
-
批准号:2291750
-
项目类别:
-
资助金额:$2.0万
-
财政年份:1993
-
负责人:KENNETH C. INGHAM
-
依托单位:
NHLBI SHARED RESEARCH FACILITY FOR MOLECULAR BIOLOGY
-
批准号:3003479
-
项目类别:
-
资助金额:$24.6万
-
财政年份:1987
-
负责人:KENNETH C. INGHAM
-
依托单位:
INTERACTIONS OF FIBRONECTIN MODULES
-
批准号:2685278
-
项目类别:
-
资助金额:$23.74万
-
财政年份:1978
-
负责人:KENNETH C. INGHAM
-
依托单位:
PHYSICAL CHEMISTRY OF THERAPEUTIC PLASMA PROTEINS
-
批准号:3336616
-
项目类别:
-
资助金额:$23.22万
-
财政年份:1978
-
负责人:KENNETH C. INGHAM
-
依托单位:
PHYSICAL CHEMISTRY OF THERAPEUTIC PLASMA PROTEINS
-
批准号:3336615
-
项目类别:
-
资助金额:$13.96万
-
财政年份:1978
-
负责人:KENNETH C. INGHAM
-
依托单位:
DOMAIN STRUCTURE AND MATRIX INTERACTIONS OF FIBRONECTIN
-
批准号:3336612
-
项目类别:
-
资助金额:$20.09万
-
财政年份:1978
-
负责人:KENNETH C. INGHAM
-
依托单位:
INTERACTIONS OF FIBRONECTIN MODULES
-
批准号:6182881
-
项目类别:
-
资助金额:$25.18万
-
财政年份:1978
-
负责人:KENNETH C. INGHAM
-
依托单位:
PHYSICAL CHEMISTRY OF THERAPEUTIC PLASMA PROTEINS
-
批准号:3336618
-
项目类别:
-
资助金额:$21.56万
-
财政年份:1978
-
负责人:KENNETH C. INGHAM
-
依托单位:
PHYSICAL CHEMISTRY OF THERAPEUTIC PLASMA PROTEINS
-
批准号:3336617
-
项目类别:
-
资助金额:$22.93万
-
财政年份:1978
-
负责人:KENNETH C. INGHAM
-
依托单位:
PHYSICAL CHEMISTRY OF THERAPEUTIC PLASMA PROTEINS
-
批准号:3336614
-
项目类别:
-
资助金额:$8.99万
-
财政年份:1978
-
负责人:KENNETH C. INGHAM
-
依托单位:
INTERACTIONS OF FIBRONECTIN MODULES
-
批准号:2028024
-
项目类别:
-
资助金额:$23.05万
-
财政年份:1978
-
负责人:KENNETH C. INGHAM
-
依托单位:
DOMAIN STRUCTURE AND MATRIX INTERACTIONS OF FIBRONECTIN
-
批准号:2215493
-
项目类别:
-
资助金额:$22.07万
-
财政年份:1978
-
负责人:KENNETH C. INGHAM
-
依托单位:
INTERACTIONS OF FIBRONECTIN MODULES
-
批准号:2901030
-
项目类别:
-
资助金额:$24.45万
-
财政年份:1978
-
负责人:KENNETH C. INGHAM
-
依托单位:
DOMAIN STRUCTURE AND MATRIX INTERACTIONS OF FIBRONECTIN
-
批准号:2215492
-
项目类别:
-
资助金额:$21.69万
-
财政年份:1978
-
负责人:KENNETH C. INGHAM
-
依托单位:
DOMAIN STRUCTURE AND MATRIX INTERACTIONS OF FIBRONECTIN
-
批准号:2215494
-
项目类别:
-
资助金额:$23.17万
-
财政年份:1978
-
负责人:KENNETH C. INGHAM
-
依托单位:
海外基金