SAR OF INTERLEUKIN 2 AND IL-2 RELATED PEPTIDES

这项研究计划的目标有两个。首先，要确定哪些是 构成白介素2一级序列的133个氨基酸残基 参与受体结合和生物活性的表达； 第二，利用这些信息设计与IL-2相关的多肽 具有潜在的治疗作用，具有激动剂和拮抗剂活性。 我们将利用重组DNA衍生蛋白、合成肽和 单抗与分析、物理和生物检测相结合 实现我们目标的第一部分的方法。然后，知道哪些地区 IL-2的重要性，我们将使用计算机辅助分子模拟来 帮助设计保持适当立体化学关系的类似物 激动剂活性或受体结合所必需的。我们还将设计 潜在的IL-2拮抗剂使用类似的技术和知识 IL-2结合细胞表面蛋白的序列。我们将做好准备和 在IL-2生物测定中纯化化合物并测定其活性 竞争性放射受体分析。

The goal of this research plan is two-fold. First, to identify which of the 133 amino acid residues comprising the interleukin 2 primary sequence participate in receptor binding and the expression of biologic activity; and second, to utilize this information to design IL-2 related peptides with potential therapeutic utility having agonist and antagonist activity. We will utilize recombinant DNA derived proteins, synthetic peptides and monoclonal antibodies combined with analytical, physical and biologic assay methods to achieve the first part of our goal. Then, knowing which regions of IL-2 are important, we will use computer assisted molecular modeling to help design analogs which retain the proper stereochemical relationships required for agonist activity or receptor binding. We will also design potential IL-2 antagonists using similar techniques and the knowledge of the sequence of an Il-2 binding cell surface protein. We will prepare and purify the compounds and determine their activity in the Il-2 bioassay and competitive radioreceptor assay.