Development of Novel Screening Systems for Receptor Ligands

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Novel bioassay systems have been established for ligand screening to chemokine receptor CXCR4. Using a fluorescent CXCR4 antagonist probe, the receptor binding of potential CXCR4 ligands was quantitatively evaluated by flow cytometry. This facile approach would be applicable to the other receptors of peptide hormones and cytokines. The fluorescent SDF-1 derivatives have also been developed as novel agonist-based probes, which successfully detected the receptor internalization process of CXCR4. Furthermore, in order to investigate the bioactive conformations of CXCR4 antagonist, FC131, the structure-activity relationship study was performed using a series of alkene-type dipeptide isostere. It was demonstrated that both Tyr carbonyl oxygen and Arg N-alkyl group would predominantly contribute to the local conformations of FC131.