ABSTRACT: Bombesin receptor subtype (BRS)-3, a G-protein-coupled orphan receptor, shares 51% identity with the mammalian bombesin (Bn) receptor for gastrin-releasing peptide. There is increasing interest in BRS-3 because it is important in energy metabolism, glucose control, motility, and tumor growth. BRS-3 has low affinity for all Bn-related peptides; however, recently synthetic high-affinity agonists, [d-Tyr(6)/d-Phe(6),betaAla(11),Phe(13),Nle(14)]Bn-(6-14), were described, but they are nonselective for BRS-3 over other Bn receptors. Based on these peptides, three BRS-3-selective ligands were developed: peptide 2, [d-Tyr(6)(R)-3-amino-propionic acid(11),Phe(13),Nle(14)]Bn(6-14); peptide 3, [d-Tyr(6),(R)-Apa(11),4Cl-Phe(13),Nle(14)]Bn(6-14); and peptide 4, acetyl-Phe-Trp-Ala-His-(tBzl)-piperidine-
