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.