ANTIBODIES & RECOMBINANT DNA IN CARDIOVASCULAR RESEARCH

我们对抗体结构和功能的理解的演变 结合点已经发展到现在人们可以现实地 考虑抗体作为显著的生物学活性的试剂或药物的应用。 的特异性 与传统药物不同的是， 允许与其靶位点，抗体， 结合部位相对宽敞。 这使得许多原子间 与配体接触，允许显着的选择性以及非常高的 亲和力 细胞融合法制备抗体的研究进展 允许在一个或多个细胞中产生具有确定特异性的同质抗体， 可复制的方式。 在所提出的方案中，抗体结合位点将 作为心血管研究的主要工具。 在最基本的 水平，将解剖地高辛特异性抗体的结合位点 从而使抗体适合于 治疗用途可以通过化学合成或可替代地通过 翻译基因信息。 再次利用地高辛特异性抗体作为 模型，将检查抗体片段的药理学 临床研究中的特性。 分子特性的分辨率允许 通过抗体结合位点的特异性将被充分利用 在解剖生理学，病理生理学，和生物合成的肾素; 肾上腺素能受体的性质和纯化 抗体;并在阐明前列腺素的功能， 血管紧张素受体 所有这些项目的调查人员都有一个共同点， 研究工具抗体结合位点和联合利用设施 一个蛋白质化学和细胞融合实验室， 他们使用的试剂。

The evolution of our understanding of the structure and function of the antibody combining site has advanced to the point that one can now realistically contemplate the application of antibodies as reagents or drugs of remarkable specificity. Unlike the conventional drug, which is a small organic molecule that allows a limited number of contacts with its target site, the antibody combining site is relatively capacious. This permits numerous interatomic contacts with a ligand, allowing for remarkable selectivity as well as very high affinity. The development of cell fusion methods for producing antibodies now permits the production of homogeneous antibodies of defined specificity in a reproducible manner. In the proposed program, the antibody combining site will be investigated as a major tool in cardiovascular research. On a most basic level, the combining site of antibodies specific for digoxin will be dissected with respect to its primary structure so that antibodies suitable for therapeutic use might be produced by chemical synthesis or alternatively by translation a gene message. Again utilizing digoxin specific antibody as a model, antibody fragments will be examined with respect to their pharmacologic properties in clinical studies. The resolution of molecular properties allowed by the specificity of the antibody combining site will be utilized to advantage in the dissection of the physiology, pathophysiology, and biosynthesis of renin; in the understanding of the properties and purification of adrenergic receptor antibodies; and in the elucidation of the function of prostaglandin and angiotensin receptors. The investigators in all these projects have as a common research tool the antibody combining site and utilize conjointly the facilities of a protein chemistry and cell fusion laboratory to produce and understand the reagents that they utilize.