Article Dans Une Revue ACS Applied Bio Materials Année : 2021

A Lipidated Peptide with Mitochondrial Membrane Localization in Human A549 Lung Cells: From Enhanced Cell-Penetrating Properties to Biological Activity Mechanism

Résumé

Here, a lipidated peptide Pal-pHK-pKV with self-assembly properties and the ability to provoke the disruption of the mitochondrial voltage-dependent anion channel-1 protein (VDAC1)-hexokinase-II (HK-II) complex is reported. The effects of the peptide pHK (N-terminal 15-amino acid fragment of HK-II that specifically binds VDAC1) are compared to those of a designed biomimetic amphiphilic pHK-pKV conjugate (pHK coupled with a cell-penetrating peptide pKV) and Pal-pHK-pKV (a lipidated conjugate modified with a hydrophobic palmitic (Pal) alkyl chain). The Pal-pHK-pKV exhibits a stronger interaction with the membrane as compared to pHK-pKV, which is demonstrated by the Langmuir–Blodgett technique and two-photon excitation microscopy. The amphiphilic peptide derivatives are cytotoxic to the A549 cells, but Pal-pHK-pKV is more cytotoxic. The inhibitory effects of the pHK derivatives on the A549 cells growth are investigated through induced apoptosis pathway, depolarized mitochondrial membrane potential, inhibited glycolysis, and activated caspase. The results of the immunofluorescence evidence the specific mitochondrial targeting by those derivatives.

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hal-03861744 , version 1 (20-11-2022)

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Xinlei Zhang, Angelina Angelova, Wanfeng Sun, Fan Zhang, Na Li, et al.. A Lipidated Peptide with Mitochondrial Membrane Localization in Human A549 Lung Cells: From Enhanced Cell-Penetrating Properties to Biological Activity Mechanism. ACS Applied Bio Materials, 2021, 4 (12), pp.8277-8290. ⟨10.1021/acsabm.1c00815⟩. ⟨hal-03861744⟩
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