Modulation of the Interaction between a Peptide Ligand and a G Protein-Coupled Receptor by Halogen Atoms

Mònica Rosa, Gianluigi Caltabiano, Katy Barreto-Valer, Verónica Gonzalez-Nunez, José C. Gómez-Tamayo, Ana Ardá, Jesús Jiménez-Barbero, Leonardo Pardo, Raquel E. Rodríguez, Gemma Arsequell, Gregorio Valencia

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Abstract

© 2015 American Chemical Society. Systematic halogenation of two native opioid peptides has shown that halogen atoms can modulate peptide-receptor interactions in different manners. First, halogens may produce a steric hindrance that reduces the binding of the peptide to the receptor. Second, chlorine, bromine, or iodine may improve peptide binding if their positive σ-hole forms a halogen bond interaction with negatively charged atoms of the protein. Lastly, the negative electrostatic potential of fluorine can interact with positively charged atoms of the protein to improve peptide binding.
Original languageEnglish
Pages (from-to)872-876
JournalACS Medicinal Chemistry Letters
Volume6
Issue number8
DOIs
Publication statusPublished - 13 Aug 2015

Keywords

  • drug design
  • endomorphin-1
  • G protein-coupled receptors
  • Halogen bond
  • halogenated peptides
  • Leu-enkephalin
  • neuropeptides
  • opioid receptors

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