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Bulletin of the Korean Chemical Society (BKCS)

ISSN 0253-2964(Print)
ISSN 1229-5949(Online)
Volume 29, Number 3
BKCSDE 29(3)
March 20, 2008 

3D Quantitative and Qualitative Structure-Activity Relationships of the δ-Opioid Receptor Antagonists
Sun Chun, Jee-Young Lee*, Seong-Gu Ro, Ki-Woong Jeong, Yangmee Kim, Chang-Ju Yoon*
GPCR, Opioid receptor, Analgesic drug, Catalyst, QSAR
Antagonists of the δ-opioid receptor are effective in overcoming resistance against analgesic drugs such as morphine. To identify novel antagonists of the δ-opioid receptor that display high potency and low resistance, we performed 3D-QSAR analysis using chemical feature-based pharmacophore models. Chemical features for δ-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 δ-opioid receptor, and determine the appropriate pharmacophore to design such antagonists.
656 - 662
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