Enzymatically Formed Peptide Assemblies Sequestrate Proteins and Relocate Inhibitors to Selectively Kill Cancer Cells.

ABSTRACT: Herein, we show that an enzymatic reaction can generate peptide assemblies that sequestrate proteins to selectively kill cancer cells. A phosphopeptide bearing the antagonistic motif (AVPI) to the inhibitors of apoptotic proteins (IAPs) enters cancer cells and normal cells by caveolin-dependent endocytosis and macropinocytosis, respectively. The AVPI-bearing peptide assemblies sequestrates IAPs and releases bortezomib (BTZ), a proteasome inhibitor, in the cytosol of cancer cells, but rescues the normal cells (namely, HS-5 cells) by trafficking the BTZ into lysosomes. Alkaline phosphatase (ALP) acts as a context-dependent signal for trafficking the peptide/BTZ assemblies and selectively induces the death of the cancer cells. The assemblies of AVPI exhibit enhanced proteolytic resistance. Th

SUBMITTER: He H 

PROVIDER: S-EPMC7844580 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature