Selective ligands for the mu, delta, 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 based positional scanning format was screened in binding assays for the three opioid receptors, mu, delta, and kappa. Three different binding profiles were found. Individual peptides were synthesized representing all 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 mixture-based combinatorial libraries to identify distinctly different ligands for closely related receptors.