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

Angewandte Chemie
Hongjian HeBing Xu

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. This work, which utilizes the difference in endocytic uptake of enzymatically formed peptide assemblies to selectively kill cancer cells, promises a new way to develop selective cancer therapeutics.

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Citations

Jan 30, 2021·Cell Reports. Physical Science·Hongjian HeBing Xu
Dec 24, 2020·Chemical Communications : Chem Comm·Li-Song ZhangZhi-Song Zhang
Aug 20, 2020·Chemical Reviews·Hongjian HeBing Xu
Jun 19, 2021·Nano Letters·Mingming LiZhilin Yu
Jul 31, 2021·Current Opinion in Chemical Biology·Tania L Lopez-Silva, Joel P Schneider
Jul 29, 2021·Biomaterials Science·Ning LiuZhanwei Zhou

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