Abdelfattah Faouzi, Haoqing Wang, Saheem A Zaidi, Jeffrey F DiBerto, Tao Che, Qianhui Qu, Michael J Robertson, Manish K Madasu, Amal El Daibani, Balazs R Varga, Tiffany Zhang, Claudia Ruiz, Shan Liu, Jin Xu, Kevin Appourchaux, Samuel T Slocum, Shainnel O Eans, Michael D Cameron, Ream Al-Hasani, Ying Xian Pan, Bryan L Roth, Jay P McLaughlin, Georgios Skiniotis, Vsevolod Katritch, Brian K Kobilka, Susruta Majumdar
Mu-opioid receptor (µOR) agonists such as fentanyl have long been used for pain management, but are considered a major public health concern owing to their adverse side effects, including lethal overdose1 . Here, in an effort to design safer therapeutic agents, we report an approach targeting a conserved sodium ion-binding site2 found in µOR3 and many other class A G-protein-coupled receptors with bitopic fentanyl derivatives that are functionalized via a linker with a positively charged guanidino group...
November 30, 2022: Nature