Molecular basis for high affinity and selectivity of peptide antagonist, Bantag-1, for the orphan BB3 receptor.

@article{Nakamura2016MolecularBF,
  title={Molecular basis for high affinity and selectivity of peptide antagonist, Bantag-1, for the orphan BB3 receptor.},
  author={Taichi Nakamura and Irene Ramos-{\'A}lvarez and Tatiana Iordanskaia and Paola Moreno and Samuel A. Mantey and Robert T. Jensen},
  journal={Biochemical pharmacology},
  year={2016},
  volume={115},
  pages={
          64-76
        }
}
Bombesin-receptor-subtype-3 (BB3 receptor) is a G-protein-coupled-orphan-receptor classified in the mammalian Bombesin-family because of high homology to gastrin-releasing peptide (BB2 receptor)/neuromedin-B receptors (BB1 receptor). There is increased interest in BB3 receptor because studies primarily from knockout-mice suggest it plays roles in energy/glucose metabolism, insulin-secretion, as well as motility and tumor-growth. Investigations into its roles in physiological/pathophysiological… 
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These results demonstrate that Val101, His107, Gly112, and Arg127 in the EC2/adjacent upper TMs of BRS-3 are critical for the high BRS3 selectivity of peptides 4 and 1, and amino-aromatic ligand/receptor interactions with peptide 4 arecritical for both binding and activation.
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It is demonstrated that Thr297, Phe302, and Ser305 of the fourth EC domain of GRPR are the critical residues for determining GRPR selectivity and suggest that both receptor-ligand cation-π interactions and hydrogen bonding are important for their high affinity interaction.
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TLDR
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ML-18 is a nonpeptide BRS-3 antagonist that should serve as a template to improve potency and selectivity and inhibit the proliferation of lung cancer cells.
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