Аннотация:
MDMB-FUBINACA is an indazole-based synthetic cannabinoid, a derivative of AB-FUBINACA in which the terminal aminocarbonyl moiety is replaced by a methyl ester group and the isobutyl moiety is substituted with a tert-butyl group. The physiological and toxicological properties of this compound have not been determined. However, docking of MDMB-FUBINACA with human cannabinoid receptor-1 is a key feature of its physiological action. Structural features of human cannabinoid receptor-1 (hCB1) transmembrane helix 7 (TMH7) and helix 8 (H8) [hCB1(TMH7/H8)] include, from the peptide's amino terminus, a hydrophobic alpha-helix (TMH7); a loop-like, 11 residue segment featuring a pronounced Pro-kink within the conserved NPxxY motif; a short amphipathic alpha-helix (H8) orthogonal to TMH7 with cationic and hydrophobic amino-acid clusters; and an unstructured C-terminal end. The hCB1(TMH7/H8) NMR solution structure suggests multiple electrostatic amino-acid interactions, including an intrahelical H8 salt bridge and a hydrogen-bond network involving the peptide's loop-like region. Potential cation-pi and cation-phenolic OH interactions between Y(397) in the TMH7 NPxxY motif and R(405) in H8 are identified as candidate structural forces promoting interhelical microdomain formation. This microdomain may function as a flexible molecular hinge during ligand-induced hCB1 conformer transitions. AutoDock Vina is an open-source program for doing molecular docking. It was designed and implemented by Dr. Oleg Trott in the Molecular Graphics Lab at The Scripps Research Institute.
Ключевые слова:
MDMB-FUBINACA, MDMB(N)-BZ-F, MDMB(N)-FUB, cannabimimetic, cannabinoid receptor CB1, molecular docking