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 cytokins similar to Interleukin 6 (IL-6), that is Oncostatin M (OSM), Leukemia Inhibitory Factor (LIF), Ciliary Neurotrophic Factor (CNTF) and Interleukin 11 (IL-11), induce formation of a receptor complex of which the membrane molecule gp 130 is a part. It is thus possible to formulate the hypothesis that two different surfaces of the protein (in this class of hormones), known as site 1 and site 2, bind to two different molecules: site 1 to the specific receptor and site 2 to gp 130. The invention allows the identification of these sites and the isolation of variants having, with respect to the wild hormone, a greater affinity for the specific receptor (superagonists and superantagonists) or affinity for gp 130 reduced or abolished (antagonists and superantagonists). The figure shows the construct pHen DELTA hIL-6 and the production of phasmidic particles that can be used to select agonists of Interleukin 6.