Identification of drug complementary combinatorial libraries

A method of identifying a ligand which can mediate the biological activity of a target protein via inhibition of the binding of a target protein to a binding partner ligand which comprises

• (a) screening a first combinatorial library comprising a plurality of first member ligands for binding to the target protein, thereby identifying one or more target-binding ligands,
• (b) screening a second library comprising a plurality of second member ligands for the ability to inhibit the binding of one or more of said target-binding ligands to said target protein, thereby obtaining one or more inhibitory ligands, and
• (c) determining which of the inhibitory ligands can mediate a biological activity of the target protein,
• said inhibitory ligand thereby being identified as an activity-mediating ligand,
• in which the target protein is a nuclear receptor of the steroid receptor family,
• in which the first library is composed of peptides, the peptides do not comprise antibody-like domains, at least one peptide is characterized by an amino acid sequence comprising the Leu-Xaa-Xaa-Leu-Leu (Seq. ID. NO.121) sequence motif, wherein Xaa represents any genetically encoded amino acid, and the peptides are displayed on phage, and
• in which the second library is a non-biopolymeric combinatorial library.