Chemoproteomic fishing identifies arzanol as a positive modulator of brain glycogen phosphorylase

Abstract

The interactome of arzanol was investigated by MS-based chemical proteomics, a pioneering technology for small molecule target discovery. Brain glycogen phosphorylase (bGP), a key regulator of glucose metabolism so far refractory to small molecule modulation, was identified as the main high-affinity target of arzanol. Competitive affinity-based proteomics, DARTS, molecular docking, surface plasmon resonance and in vitro biological assays provided molecular mechanistic insights into the arzanol–enzyme interaction, qualifying this positive modulator of bGP for further studies in the realm of neurodegeneration and cancer.