METHOD OF IDENTIFYING CONFORMATION-SENSITIVE BINDING PEPTIDES AND USES THEREOF

摘要

Peptides which bind a cellular (surface or intracellular) receptor, such as a nuclear receptor, may be identified by screening a combinatorial peptide library presented in the form of cells each of which coexpress one member peptide and the receptor, together with a signal producing system for reporting binding. A "two-hybrid" assay is of particular interest. The screen may be carried out in the presence of a ligand, in particular, an exogenous ligand. If this screening is carried out for a plurality of different receptor conformations, then this library screening will also serve to identify conformation-specific peptides for the receptor, which may then be used in a panel for "fingerprinting"query compounds as to their ability to interact with the receptor in the presence of each of the panel peptides. These fingerprints may be compared to those of reference compounds with known biological activities mediated by that receptor.