Angewandte Chemie (International ed.), 2020-09, Vol.59 (38), p.16445-16450
International ed. in English, 2020
Details
- Autor(en) / Beteiligte
- Titel
- Enzymatically Formed Peptide Assemblies Sequestrate Proteins and Relocate Inhibitors to Selectively Kill Cancer Cells
- Ist Teil von
- Angewandte Chemie (International ed.), 2020-09, Vol.59 (38), p.16445-16450
- Auflage
- International ed. in English
- Ort / Verlag
- Germany: Wiley Subscription Services, Inc
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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. The enzymatic self‐assembly: A proapoptotic‐peptide–bortezomib (BTZ) assembly enters cancer cells by caveolin‐dependent endocytosis and is dephosphorylated by alkaline phosphatase (ALP), releasing BTZ. The peptides sequestrate the inhibitors of apoptotic proteins (IAPs), promoting cell death. In contrast, this assembly enters normal cells by macropinocytosis and is transported to the lysosome, reducing side effects of cancer therapy for normal cells.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1433-7851eISSN: 1521-3773DOI: 10.1002/anie.202006290Titel-ID: cdi_proquest_miscellaneous_2412221794
- Format
- –
- Schlagworte
- Alkaline phosphatase, Alkaline Phosphatase - metabolism, Antineoplastic Agents - chemistry, Antineoplastic Agents - metabolism, Antineoplastic Agents - pharmacology, Apoptosis, Assemblies, Bortezomib, Bortezomib - chemistry, Bortezomib - metabolism, Bortezomib - pharmacology, Cancer, Caveolin, Cell death, Cell Proliferation - drug effects, Cell Survival - drug effects, Cytosol, Drug Screening Assays, Antitumor, Endocytosis, HeLa Cells, Humans, Inhibitors, Lysosomes, Molecular Structure, Peptides, Peptides - chemistry, Peptides - metabolism, Peptides - pharmacology, Proteasome Endopeptidase Complex - metabolism, Proteasome inhibitors, Proteasome Inhibitors - chemistry, Proteasome Inhibitors - metabolism, Proteasome Inhibitors - pharmacology, Protein transport, Proteins, Proteolysis, Tumor Cells, Cultured