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 N,N-dimethyl-l-alanine ester and the C34 N-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.

Automated summary

Inspired by natural products based on protein-protein interactions (PPI), structurally-simplified analogs of aplyronine A were developed, with one analog showing potent actin-depolymerizing activity. These analogs are versatile actin-affinity tags that can accelerate research on the mode of action related to cytoskeletal dynamics and the development of PPI-based drug leads.