CHARACTERIZATION OF HEMATIN DERIVED ANTICOAGULANT
CHARACTERIZATION OF HEMATIN DERIVED ANTICOAGULANT
批准号:
3345351
负责人:
ROBERT L JONES
金额:
$11.17万
依托单位:
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 1988-09-29
关键词:
affinity chromatography anticoagulants blood /lymphatic pharmacology blood coagulation tests chemical structure drug administration routes drug design /synthesis /production drug metabolism ferriheme gastrointestinal drug absorption heme high performance liquid chromatography nuclear magnetic resonance spectroscopy oxidation pharmacokinetics porphyrin metabolism thrombosis ultraviolet spectrometry
中文摘要
本建议书中描述的项目旨在定义
血红素衍生蛋白的生化、生物学和药理学意义
抗凝剂(HDA)。HDA在体外可延长凝血时间
在活体内。HDA是一种衍生品或降解产物
当血红素被允许站在溶液中或当它被注入到
老鼠。HDA将从体外和体内得到纯化和鉴定
来源通过层析和光谱技术。这将考验
假设HDA是血红素(血红素)的单一衍生物,这是
能够与凝血蛋白相互作用,产生深刻的
功能效应。HDA与特异体相互作用的机理
纤维蛋白原、凝血酶和因子VIII:C的定义如下
测定结合亲和力及对酶功能的影响
天然和合成底物。紫外可见光谱的具体技术
光谱学、平衡透析和铁结合拮抗
化合物将检验是否涉及铁或微量金属的假设
在HDA与凝血蛋白的相互作用中。制作和制作
HDA在体内的作用机制将通过分离的肝血红素来确定
代谢系统和整个动物。这将检验这一假设
HDA是血红素的代谢产物,其作用机制与
这是在体外观察到的。具体技术涉及放射性同位素和
药理探头。最后,HDA的药理潜力将是
由利用放射性标记进行的药代动力学和疗效研究确定
HDA和各种给药途径。完成这些研究后,
明确HDA的生化、生理和药理学意义。
英文摘要
The project described in this proposal is designed to define the
biochemical, biologic and pharmacologic significance of hematin-derived
anticoagulant (HDA). HDA produces prolongation of clotting times in vitro
and in vivo. HDA is a derivative or degradation product which is produced
when hematin is allowed to stand in solution or when it is infused into
rats. HDA will be purified and identified from in vitro and in vivo
sources by chromatographic and spectroscopic techniques. This will test
the hypothesis that HDA is a single derivative of hematin (heme) which is
capable of interacting with coagulation proteins to produce profound
functional effects. The mechanism of interaction of HDA with the specific
proteins fibrinogen, thrombin and factor VIII:C will be defined by
determining binding affinities and effects on enzymatic function with
natural and synthetic substrates. The specific techniques of UV-Vis
spectroscopy, equilibrium dialysis and antagonism with iron binding
compounds will test the hypothesis that iron or a trace metal is involved
in the interaction of HDA with clotting proteins. The production and
mechanism of HDA in vivo will be defined with isolated hepatic heme
metabolic systems and whole animals. This will test the hypothesis that
HDA is a metabolic product of heme and that the mechanism is identical to
that seen in vitro. Specific techniques involve radioisotope and
pharmacologic probes. Finally, the pharmacologic potential of HDA will be
determined by pharmacokinetic and efficacy studies utilizing radiolabelled
HDA and various routes of administration. Completion of these studies will
define the biochemical, physiologic and pharmacologic significance of HDA.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
Thrombophlebitis and disturbed hemostasis following administration of intravenous hematin in normal volunteers.
正常志愿者静脉注射血红素后出现血栓性静脉炎和止血障碍。
DOI:
10.1016/s0002-9343(88)80092-5
发表时间:
1988
期刊:
The American journal of medicine
影响因子:
--
作者:
[Simionatto,CS, Cabal,R, Jones,RL, Galbraith,RA]
通讯作者:
Galbraith,RA
GRANTS FOR PREDOCTORAL TRAINING IN FAMILY MEDICINE
-
批准号:2536255
-
项目类别:
-
资助金额:$0.0万
-
财政年份:1997
-
负责人:ROBERT L JONES
-
依托单位:
CHARACTERIZATION OF HEMATIN DERIVED ANTICOAGULANT
-
批准号:3345348
-
项目类别:
-
资助金额:$11.22万
-
财政年份:1985
-
负责人:ROBERT L JONES
-
依托单位:
CHARACTERIZATION OF HEMATIN DERIVED ANTICOAGULANT
-
批准号:3345346
-
项目类别:
-
资助金额:$7.12万
-
财政年份:1985
-
负责人:ROBERT L JONES
-
依托单位:
CHARACTERIZATION OF HEMATIN DERIVED ANTICOAGULANT
-
批准号:3345350
-
项目类别:
-
资助金额:$1.15万
-
财政年份:1985
-
负责人:ROBERT L JONES
-
依托单位:
CHEMISTRY AND METABOLISM OF A MAMMALIAN SIDEROPHOR
-
批准号:3152292
-
项目类别:
-
资助金额:$11.15万
-
财政年份:1983
-
负责人:ROBERT L JONES
-
依托单位:
CHEMICAL & METABOLIC STUDIES OF A MAMMALIAN SIDEROPHORE
-
批准号:3072314
-
项目类别:
-
资助金额:$5.32万
-
财政年份:1983
-
负责人:ROBERT L JONES
-
依托单位:
CHEMICAL & METABOLIC STUDIES OF A MAMMALIAN SIDEROPHORE
-
批准号:3072315
-
项目类别:
-
资助金额:$5.37万
-
财政年份:1983
-
负责人:ROBERT L JONES
-
依托单位:
CHEMICAL & METABOLIC STUDIES OF A MAMMALIAN SIDEROPHORE
-
批准号:3071154
-
项目类别:
-
资助金额:$5.36万
-
财政年份:1983
-
负责人:ROBERT L JONES
-
依托单位:
GRANTS FOR PREDOCTORAL TRAINING IN FAMILY MEDICINE
-
批准号:2280479
-
项目类别:
-
资助金额:$0.0万
-
财政年份:1978
-
负责人:ROBERT L JONES
-
依托单位:
GRANTS FOR PREDOCTORAL TRAINING IN FAMILY MEDICINE
-
批准号:2280478
-
项目类别:
-
资助金额:$0.0万
-
财政年份:1978
-
负责人:ROBERT L JONES
-
依托单位:
PREDOCTORAL TRAINING GRANT IN FAMILY MEDICINE
-
批准号:3007959
-
项目类别:
-
资助金额:$0.0万
-
财政年份:1978
-
负责人:ROBERT L JONES
-
依托单位:
PREDOCTORAL TRAINING GRANT IN FAMILY MEDICINE
-
批准号:3007965
-
项目类别:
-
资助金额:$0.0万
-
财政年份:1978
-
负责人:ROBERT L JONES
-
依托单位:
GRANTS FOR PREDOCTORAL TRAINING IN FAMILY MEDICINE
-
批准号:3007963
-
项目类别:
-
资助金额:$0.0万
-
财政年份:1978
-
负责人:ROBERT L JONES
-
依托单位:
GRANTS FOR PREDOCTORAL TRAINING IN FAMILY MEDICINE
-
批准号:3007964
-
项目类别:
-
资助金额:$0.0万
-
财政年份:1978
-
负责人:ROBERT L JONES
-
依托单位:
GRANTS FOR PREDOCTORAL TRAINING IN FAMILY MEDICINE
-
批准号:3007960
-
项目类别:
-
资助金额:$0.0万
-
财政年份:1978
-
负责人:ROBERT L JONES
-
依托单位:
GRANTS FOR PREDOCTORAL TRAINING IN FAMILY MEDICINE
-
批准号:3007958
-
项目类别:
-
资助金额:$0.0万
-
财政年份:1978
-
负责人:ROBERT L JONES
-
依托单位:
PREDOCTORAL TRAINING GRANT IN FAMILY MEDICINE
-
批准号:3007966
-
项目类别:
-
资助金额:$0.0万
-
财政年份:1978
-
负责人:ROBERT L JONES
-
依托单位:
DIABETES MELLITUS AND THROMBOSIS
-
批准号:3948350
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:ROBERT L JONES
-
依托单位:
HEPATIC FUNCTION
-
批准号:3763742
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:ROBERT L JONES
-
依托单位:
IRON METABOLISM AND THROMBOSIS
-
批准号:3884918
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:ROBERT L JONES
-
依托单位:
海外基金