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Arzanol Biomolecular Targets - 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 molecules 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, and in vitro biological assays provided molecular mechanistic insights on the arzanol-enzyme interaction, qualifying this positive modulator of bGP for further studies in the realm of neurodegeneration and cancer.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Hela Cell

DISEASE(S): Breast Cancer

SUBMITTER: Maria Chiara Monti

LAB HEAD: Maria Chiara Monti

PROVIDER: PXD011170 | Pride | 2019-03-25

REPOSITORIES: Pride

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

Del Gaudio Federica F Pollastro Federica F Mozzicafreddo Matteo M Riccio Raffaele R Minassi Alberto A Monti Maria Chiara MC

Chemical communications (Cambridge, England) 20181101 91

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-e ...[more]

PMID: 30375590

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