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.
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