TY  - JOUR
AU  - Dosen-Miovic, Ljiljana
AU  - Ivanović, Milovan
AU  - Micovic, Vuk
PY  - 2007
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/852
AB  - Fentanyl 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.
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - Location of the hydrophobic pocket in the binding site of fentanyl analogs in the mu-opioid receptor
VL  - 72
IS  - 7
SP  - 643
EP  - 654
DO  - 10.2298/JSC0707643D
ER  - 

@article{
author = "Dosen-Miovic, Ljiljana and Ivanović, Milovan and Micovic, Vuk",
year = "2007",
abstract = "Fentanyl 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.",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "Location of the hydrophobic pocket in the binding site of fentanyl analogs in the mu-opioid receptor",
volume = "72",
number = "7",
pages = "643-654",
doi = "10.2298/JSC0707643D"
}

Dosen-Miovic, L., Ivanović, M.,& Micovic, V.. (2007). Location of the hydrophobic pocket in the binding site of fentanyl analogs in the mu-opioid receptor. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 72(7), 643-654.
https://doi.org/10.2298/JSC0707643D

Dosen-Miovic L, Ivanović M, Micovic V. Location of the hydrophobic pocket in the binding site of fentanyl analogs in the mu-opioid receptor. in Journal of the Serbian Chemical Society. 2007;72(7):643-654.
doi:10.2298/JSC0707643D .

Dosen-Miovic, Ljiljana, Ivanović, Milovan, Micovic, Vuk, "Location of the hydrophobic pocket in the binding site of fentanyl analogs in the mu-opioid receptor" in Journal of the Serbian Chemical Society, 72, no. 7 (2007):643-654,
https://doi.org/10.2298/JSC0707643D . .