A Strategy for Discovering Heterochiral Bioactive Peptides by Using the OB2n P Library and SPOTs Method.

d-Amino acid containing peptides are promising as drug lead compounds because of their expected higher stability in vivo. A heterochiral random peptide library called the one-bead-2n -peptide (OB2n P) library, which can display 2n peptide diastereomers per bead, has been developed. Through screening of the OB2n P library and subsequent binding assay among the peptide diastereomers synthesized in parallel by means of the SPOTs method, new heterochiral mimotopes for the anti-β-endorphin monoclonal antibody have been obtained. One mimotope was a new ligand for the μ-opioid receptor. The screening strategy enabled d-amino acid containing drug leads to be obtained efficiently by expanding searchable chemical space without increasing the experimental scale.