SAR OF INTERLEUKIN 2 AND IL-2 RELATED PEPTIDES

这项研究计划的目标是双重的。 首先，要确定哪些 包含白细胞介素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IL-2相关肽 具有激动剂和拮抗剂活性的潜在治疗用途。 我们将利用重组DNA衍生的蛋白质、合成肽和 单克隆抗体结合分析、物理和生物测定 实现第一部分目标的方法。 然后，知道哪些区域 的IL-2是重要的，我们将使用计算机辅助分子建模， 帮助设计保留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。 我们会做好准备， 纯化化合物并在IL-2生物测定中测定其活性， 竞争性放射受体测定。

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.