@article{SpahnDelVecchioLabuzetal.2017, author = {Spahn, Viola and Del Vecchio, Giovanna and Labuz, Dominika and Rodriguez-Gaztelumendi, Antonio and Massaly, N. and Temp, Julia and Durmaz, Vedat and Sabri, P. and Reidelbach, Marco and Machelska, Halina and Weber, Marcus and Stein, Christoph}, title = {A nontoxic pain killer designed by modeling of pathological receptor conformations}, volume = {355}, journal = {Science}, number = {6328}, doi = {10.1126/science.aai8636}, pages = {966 -- 969}, year = {2017}, language = {en} } @article{SpahnDelVecchioRodriguezGaztelumendietal.2018, author = {Spahn, Viola and Del Vecchio, Giovanna and Rodriguez-Gaztelumendi, Antonio and Temp, Julia and Labuz, Dominika and Kloner, Michael and Reidelbach, Marco and Machelska, Halina and Weber, Marcus and Stein, Christoph}, title = {Opioid receptor signaling, analgesic and side effects induced by a computationally designed pH-dependent agonist}, volume = {8}, journal = {Scientific Reports}, publisher = {Springer Nature}, pages = {8965}, year = {2018}, abstract = {Novel pain killers without adverse effects are urgently needed.}, language = {en} } @article{DelVecchioLabuzTempetal.2019, author = {Del Vecchio, Giovanna and Labuz, Dominika and Temp, Julia and Seitz, Viola and Kloner, Michael and Negrete, Roger and Rodriguez-Gaztelumendi, Antonio and Weber, Marcus and Machelska, Halina and Stein, Christoph}, title = {pKa of opioid ligands as a discriminating factor for side effects}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-55886-1}, pages = {19344}, year = {2019}, abstract = {The non-selective activation of central and peripheral opioid receptors is a major shortcoming of currently available opioids. Targeting peripheral opioid receptors is a promising strategy to preclude side effects. Recently, we showed that fentanyl-derived μ-opioid receptor (MOR) agonists with reduced acid dissociation constants (pKa) due to introducing single fluorine atoms produced injury-restricted antinociception in rat models of inflammatory, postoperative and neuropathic pain. Here, we report that a new double-fluorinated compound (FF6) and fentanyl show similar pKa, MOR affinity and [35S]-GTPγS binding at low and physiological pH values. In vivo, FF6 produced antinociception in injured and non-injured tissue, and induced sedation and constipation. The comparison of several fentanyl derivatives revealed a correlation between pKa values and pH-dependent MOR activation, antinociception and side effects. An opioid ligand's pKa value may be used as discriminating factor to design safer analgesics.}, language = {en} } @article{TempLabuzNegreteetal.2019, author = {Temp, Julia and Labuz, Dominika and Negrete, Roger and Sunkara, Vikram and Machelska, Halina}, title = {Pain and knee damage in male and female mice in the medial meniscal transection-induced osteoarthritis}, journal = {Osteoarthritis and Cartilage}, doi = {10.1016/j.joca.2019.11.003}, year = {2019}, language = {en} }