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dc.creatorDosen-Miovic, Ljiljana
dc.creatorIvanović, Milovan
dc.creatorMicovic, Vuk
dc.date.accessioned2018-11-22T00:11:10Z
dc.date.available2018-11-22T00:11:10Z
dc.date.issued2007
dc.identifier.issn0352-5139
dc.identifier.urihttp://cherry.chem.bg.ac.rs/handle/123456789/852
dc.description.abstractFentanyl is a highly potent and clinically widely used narcotic analgesic. The synthesis of its analogs remains a challenge in an attempt to develop highly selective mu-opioid receptor agonists with specific pharmacological properties. In this paper, the use of flexible molecular docking of several specific fentanyl analogs to the mu-opioid receptor model, in order to test the hypothesis that the hydrophobic pocket accommodates alkyl groups at position 3 of the fentanyl skeleton, is described. The stereoisomers of the following compounds were studied: cis- and trans-3-methylfentanyl. 3.3-dimethylfentanyl. cis- and trans-3-ethylfentanyl, cis- and trans-3-propylfentanyl, cis-3-isopropylfentanyl and cis-3-benzylfentanyl. The optimal position and orientation of these fentanyl analogs in the binding pocket of the mu-receptor, explaining their enantiospecific potency, were determined. It was found that the 3-alkyl group of cis-3R,4S and trans-3S,4S stereoisomers of all the active compounds occupies the hydrophobic pocket between TM5, TM6 and TM7, made LIP of the amino acids Trp318 (TM7), Ile322 (TM7), 1001 (TM6) and Phe237 (TM5). However, the fact that this hydrophobic pocket can also accommodate the bulky 3-alkyl substituents of the two inactive Compounds: cis-3-isopropylfentanyl, and cis-3-benzylfentanyl, indicates that this hydrophobic pocket in the employed receptor model is probably too large.en
dc.publisherSerbian Chemical Soc, Belgrade
dc.rightsopenAccess
dc.sourceJournal of the Serbian Chemical Society
dc.subjectmolecular modelingen
dc.subjectfentanyl analogsen
dc.subjectligand-receptor interactionsen
dc.subjectdocking simulationen
dc.titleLocation of the hydrophobic pocket in the binding site of fentanyl analogs in the mu-opioid receptoren
dc.typearticle
dc.rights.licenseBY-NC-ND
dcterms.abstractДосен-Миовиц, Љиљана; Ивановић, Милован; Мицовиц, Вук;
dc.citation.volume72
dc.citation.issue7
dc.citation.spage643
dc.citation.epage654
dc.identifier.wos000248193600002
dc.identifier.doi10.2298/JSC0707643D
dc.citation.other72(7): 643-654
dc.citation.rankM23
dc.type.versionpublishedVersion
dc.identifier.scopus2-s2.0-34447512873
dc.identifier.rcubKon_1805


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