SELECTIVE LIGANDS FOR THE MU-OPIOID, DELTA-OPIOID, AND KAPPA-OPIOID RECEPTORS IDENTIFIED FROM A SINGLE MIXTURE BASED TETRAPEPTIDE POSITIONAL SCANNING COMBINATORIAL LIBRARY

A combinatorial library of 6,250,000 tetrapeptides in the mixture base d positional scanning format was screened in binding assays for the th ree opioid receptors, mu, delta, and kappa, Three different binding pr ofiles were found. Individual peptides were synthesized representing a ll possible combinations of the active amino acids identified from the screening data. New, highly active peptides selective for each of the three receptors were chosen. This study demonstrates the power of mix ture-based combinatorial Libraries to identify distinctly different li gands for closely related receptors.