Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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3D Quantitative and Qualitative Structure-Activity Relationships of the δ -Opioid Receptor Antagonists

  • Chun, Sun (Department of Chemistry, The Catholic University of Korea) ;
  • Lee, Jee-Young (Department of Bioscience and Biotechnology, and Bio/Molecular Informatics Center, Konkuk University) ;
  • Ro, Seong-Gu (Department of Chemistry, The Catholic University of Korea) ;
  • Jeong, Ki-Woong (Department of Bioscience and Biotechnology, and Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Yang-Mee (Department of Bioscience and Biotechnology, and Bio/Molecular Informatics Center, Konkuk University) ;
  • Yoon, Chang-Ju (Department of Chemistry, The Catholic University of Korea)
  • Published : 2008.03.20
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Abstract

Antagonists of the d -opioid receptor are effective in overcoming resistance against analgesic drugs such as morphine. To identify novel antagonists of the d -opioid receptor that display high potency and low resistance, we performed 3D-QSAR analysis using chemical feature-based pharmacophore models. Chemical features for d -opioid receptor antagonists were generated using quantitative (Catalyst/HypoGen) and qualitative (Catalyst/HipHop) approaches. For HypoGen analysis, we collected 16 peptide and 16 non-peptide antagonists as the training set. The best-fit pharmacophore hypotheses of the two antagonist models comprised identical features, including a hydrophobic aromatic (HAR), a hydrophobic (HY), and a positive ionizable (PI) function. The training set of the HipHop model was constructed with three launched opioid drugs. The best hypothesis from HipHop included four features: an HAR, an HY, a hydrogen bond donor (HBD), and a PI function. Based on these results, we confirm that HY, HAR and PI features are essential for effective antagonism of the d -opioid receptor, and determine the appropriate pharmacophore to design such antagonists.

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