Discovery of Supra-Bivalent GSK3β Inhibitory Peptides Containing an ATP-Mimetic Amino Acid

a substrate-competitive site and an unexpected knob-into-hole-like conformation of the macrocycle, and thus, they act as "supra-bivalent" kinase inhibitors. This unique binding mode conferred both potency and selectivity toward GSK3β. This work demonstrated that our strategy using the warhead amino acid Z is effective in obtaining specific GSK3β inhibitors, which is likely expandable to other PK families.