The C29-C34 parts of antitumor macrolide aplyronine A serve as versatile actin-affinity tags.

Anticancer drug development inspired by natural products based on protein-protein interactions (PPI) is a promising strategy. We developed structurally-simplified C29-C34 side-chain analogs of aplyronine A (ApA), an antitumor marine macrolide. Among them, the analog possessing the C23 acyloxy group, the C29 ,-dimethyl-L-alanine ester and the C34 -methyl enamide showed potent actin-depolymerizing activity. Binding kinetics, molecular docking, and affinity-purification experiments revealed that they are versatile actin-affinity tags to accelerate studies on the mode of action related to cytoskeletal dynamics and the development of PPI-based drug leads.