A METHODOLOGY FOR SELECTING SUPERAGONISTS, ANTAGONISTS AND SUPERANTAGONISTS OF HORMONES WHOSE RECEPTOR COMPLEX INCLUDES GP 130

摘要

It has been found that the ligands of the group of cytokinssimilar to Interleukin 6 (IL-6), that is Oncostatin M (OSM), LeukemiaInhibitory Factor (LIF), Ciliary Neurotrophic Factor (CNTF) andInterleukin 11 (IL-11), induce formation of a receptor complexof which the membrane molecule gp 130 is a part. It is thuspossible to formulate the hypothesis that two different surfaces ofthe protein (in this class of hormones), known as site 1 and site 2bind to two different molecules: site 1 to the specific receptor andsite 2 to gp 130. The invention allows the identification of thesesites and the isolation of variants having, with respect to the wildhormone, a greater affinity for the specific receptor (superagonistsand superantagonists) or affinity for gp 130 reduced or abolished(antagonists and superantagonists). The figure shows the constructpHen.DELTA. hIL-6 and the production of phasmidic particles that can beused to select agonists of Interleukin 6.