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J Biol Chem, Vol. 273, Issue 30, 18848-18856, July 24, 1998

Selective Ligands for the µ, delta , and kappa  Opioid Receptors Identified from a Single Mixture Based Tetrapeptide Positional Scanning Combinatorial Library

Colette T. Dooley, Phibun Ny, Jean M. BidlackDagger , and Richard A. Houghten

From the Torrey Pines Institute for Molecular Studies, San Diego, California 92121 and the Dagger  Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York 14642

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, µ, 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.

Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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