CREATION AND FUNCTIONAL SCREENING OF A MULTIUSE PEPTIDE LIBRARY

Studies of functional interactions between transmembrane proteins such as G-protein-coupled receptors and ligands would benefit from the abi lity to utilize synthetic molecule libraries. This is realized here by the construction and application of a multi use combinatorial peptide library (MUPL). Peptides are liberated from their supports in a dry s tate so that the problem of signal interference due-to mixing of pepti de molecules, particularly agonists and antagonists, is avoided. In ad dition, the peptides are released from their supports in a controlled manner so that fractions are available for multiple independent tests, thus eliminating the need for iterative library analysis and resynthe sis. The MUPL concept was validated with a functional screen which det ects agonists to G-protein-coupled receptors and led to the discovery of new ligands. It is expected that combining MUPLs with functional as says will enhance both basic scientific research and the rates of drug discovery and development.