Abstract: The present invention provides common ligand mimics that act as common ligands for a receptor family. The present invention also provides bi-ligands containing these common ligand mimics. Bi-ligands of the invention provide enhanced affinity and/or selectivity of ligand binding to a receptor or receptor family through the synergistic action of the common ligand mimic and specificity ligand that compose the bi-ligand. The present invention also provides combinatorial libraries containing the common ligand mimics and bi-ligands of the invention. Further, the present invention provides methods for manufacturing the common ligand mimics and bi-ligands of the invention and methods for assaying the combinatorial libraries of the invention.

Abstract: The invention provides a method of identifying a population of bi-ligands to receptors in a receptor family. The method can include the steps of generating a first population of molecules comprising a specificity ligand having binding activity for a receptor in a receptor family, the specificity ligand attached to a first plurality of chemical moieties at a position on the specificity ligand to direct the specificity ligand to a specificity site and the chemical moieties to a conserved site of the receptor; screening the population of molecules for binding to the receptor; and identifying a bi-ligand having increased binding activity for the receptor relative to the specificity ligand alone, thereby identifying a common ligand having binding activity for the receptor. The method can further include the steps of generating a second population of molecules comprising the common ligand attached to a second plurality of chemical moieties.