Creation and functional screening of a multi-use peptide library.

Abstract

Studies of functional interactions between transmembrane proteins such as G-protein-coupled receptors and ligands would benefit from the ability 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 state so that the problem of signal interference due to mixing of peptide molecules, particularly agonists and antagonists, is avoided. In addition, 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 resynthesis. The MUPL concept was validated with a functional screen which detects agonists to G-protein-coupled receptors and led to the discovery of new ligands. It is expected that combining MUPLs with functional assays will enhance both basic scientific research and the rates of drug discovery and development.