CONFORMATIONS OF LIGANDS AT ANTIBODY BINDING SITES
抗体结合位点的配体构象
基本信息
- 批准号:3396425
- 负责人:
- 金额:$ 9.46万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1979
- 资助国家:美国
- 起止时间:1979-07-01 至 1986-11-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
This research will introduce tools offered by contemporary monoclonal
antibody (Mab) technology into physical studies of ligand-macromolecular
binding. The advantageous use of the large quantities of structurally
homogeneous antibody binding sites available in the form of Fab fragments
of monoclonal immunoglobulins forms the basis of the work. We plan a
series of experiments which are aimed at elucidating, in submolecular
detail, the binding of some biologically functional haptens to monoclonal
antibodies raised against them and their structural analogs. The two
haptenic systems chosen for initial study are the opiates and the
chemotactic tripeptides. In preliminary work we have obtained 4 lines of
monoclonal antibodies directed against pharmacologically important epitopes
on morphine and have demonstrated their low dissociation constants from
morphine and their differential cross-reactivities to opiate agonists and
antagonists. One of our collaborators has done similar work in the
chemotactic tripeptide system and this project has now been taken over into
our laboratory. The physical methods of choice are high frequency nuclear
magnetic resonance for solution studies and neutron diffraction for
crystallized hapten-Fab complexes. In solution, using information from
microscopic acidity constants, chemical shifts and proton-proton Nuclear
Overhauser Effects for resonances from both haptens and immunoglobulin
fragments we will form proximity maps connecting residues in immunoglobulin
folds with atoms on the haptens. With the aid of specifically deuterated
derivatives of the haptens we will determine their conformations at their
own and cross-reacting binding sites using difference neutron diffraction
performed on crystalline complexes. This work will be correlated with
amino acid sequence analysis of the hypervariable regions of the light and
heavy chains of the immunoglobulin fragments. Labeling, diffraction and
sequencing work will each be done in collaboration with expert
investigators.
This work will differ significantly from previous work on macromolecular
binding sites. We will be working with biologically functional ligands
where the Mab tool allows us to examine the fine structures of the
macromolecular binding sites in a detailed way. In addition, there is good
evidence which is emerging in several systems, including the chemotactic
peptide one, that antibody binding sites may be good models for the
cellular receptor binding sites presented to haptens, such as we will be
studying during their normal biological functions.
这项研究将介绍当代单克隆抗体提供的工具
抗体(Mab)技术进入配体大分子物理研究
绑定。 大量结构材料的有利使用
以 Fab 片段形式提供同质抗体结合位点
单克隆免疫球蛋白的研究构成了这项工作的基础。 我们计划一个
旨在阐明亚分子中的一系列实验
细节,一些具有生物功能的半抗原与单克隆抗体的结合
针对它们及其结构类似物产生的抗体。 两人
选择用于初步研究的半抗原系统是阿片类药物和
趋化三肽。 在前期工作中,我们获得了 4 行
针对药理学重要表位的单克隆抗体
吗啡并已证明其解离常数较低
吗啡及其与阿片类激动剂的不同交叉反应性
对手。 我们的一位合作者在
趋化三肽系统,该项目现已接管
我们的实验室。 选择的物理方法是高频核
用于溶液研究的磁共振和用于研究的中子衍射
结晶的半抗原-Fab 复合物。 在解决方案中,使用来自
微观酸度常数、化学位移和质子-质子核
半抗原和免疫球蛋白共振的奥弗豪瑟效应
我们将形成连接免疫球蛋白中残基的邻近图的片段
与半抗原上的原子折叠。 借助专门的氘代
半抗原的衍生物,我们将确定它们的构象
使用差异中子衍射确定自身和交叉反应的结合位点
在结晶复合物上进行。 这项工作将与
光和光高变区的氨基酸序列分析
免疫球蛋白片段的重链。 标记、衍射和
测序工作将与专家合作完成
调查人员。
这项工作将与以前的大分子工作有很大不同
结合位点。 我们将研究具有生物功能的配体
Mab 工具使我们能够检查
详细地描述了大分子结合位点。 此外,还有不错的
在几个系统中出现的证据,包括趋化
肽一,抗体结合位点可能是很好的模型
呈现给半抗原的细胞受体结合位点,例如我们将要
在正常的生物功能期间进行学习。
项目成果
期刊论文数量(0)
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{{ truncateString('JAY A GLASEL', 18)}}的其他基金
BIO-AND IMMUNO-CHEMICAL STUDIES ON OPIATE RECEPTORS
阿片受体的生物和免疫化学研究
- 批准号:
3211717 - 财政年份:1988
- 资助金额:
$ 9.46万 - 项目类别:
BIO-AND IMMUNO-CHEMICAL STUDIES ON OPIATE RECEPTORS
阿片受体的生物和免疫化学研究
- 批准号:
3211718 - 财政年份:1988
- 资助金额:
$ 9.46万 - 项目类别:
BIO-AND IMMUNO-CHEMICAL STUDIES ON OPIATE RECEPTORS
阿片受体的生物和免疫化学研究
- 批准号:
3211714 - 财政年份:1988
- 资助金额:
$ 9.46万 - 项目类别:
COMPARISON OF OPIATE/OPIOID RECEPTORS IN THE ANS AND CNS
ANS 和 CNS 中阿片/阿片类药物受体的比较
- 批准号:
3398046 - 财政年份:1983
- 资助金额:
$ 9.46万 - 项目类别:
CONFORMATIONS OF LIGANDS AT ANTIBODY BINDING SITES
抗体结合位点的配体构象
- 批准号:
3396426 - 财政年份:1979
- 资助金额:
$ 9.46万 - 项目类别:
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