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Tailor‐Made Designer Helical Peptides that Induce Mitochondrion‐Mediated Cell Death without Necrosis
Author(s) -
Nogami Kagayaki,
Takahama Kentaro,
Okushima Ayako,
Oyoshi Takanori,
Fujimoto Kazuhisa,
Inouye Masahiko
Publication year - 2014
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201402437
Subject(s) - cytosol , hela , peptide , intermembrane space , cytochrome c , mitochondrion , programmed cell death , microbiology and biotechnology , mitochondrial intermembrane space , apoptosis , cell penetrating peptide , inner mitochondrial membrane , caspase , cell , recombinant dna , biochemistry , chemistry , biophysics , biology , bacterial outer membrane , enzyme , escherichia coli , gene
Managing protein–protein interactions is essential for resolving unknown biological events at the molecular level and developing drugs. We have designed and synthesized a side‐chain‐crosslinked helical peptides based on the binding domain of a pro‐apoptotic protein (Bad) that induces programed cell death. The peptide showed high helical content and bound to its target, Bcl‐X L , more strongly than its non‐crosslinked counterparts. When HeLa cells were incubated with the crosslinked peptide, the peptide entered the cytosol across the plasma membrane. The peptide formed a stable complex with Bcl‐X L localized at the outer mitochondrial membrane, and this binding event caused the release of cytochrome c from the intermembrane space of mitochondria into the cytosol. This activated the caspase cascade: 70 % of HeLa cells died by the apoptosis pathway (without evidence of necrosis).