C-Terminal modification of polytheonamide B uncouples its dual functions in MCF-7 cancer cells

Polytheonamide B (1) is an exceptionally large peptide that forms a transmembrane ion channel. The potent cytotoxicity of 1 against MCF-7 cancer cells originates from its two ion transport functions. Compound 1 depolarizes the plasma membrane and neutralizes acidic lysosomes. Here, we describe how we uncoupled these functions by designing and synthesizing new analogues of 1.

Automated summary

Polytheonamide B (1) is a large peptide that forms a transmembrane ion channel and exhibits potent cytotoxicity against MCF-7 cancer cells. The functions of depolarizing the plasma membrane and neutralizing acidic lysosomes have been uncoupled by designing and synthesizing new analogues of 1.