Peptide name : pFL-N-Ter-TAT

Source/Organism : Analogue of N-terminal fragment of the VDAC1 protein

Linear/Cyclic : Linear

Chirality : L

Peptide length: Not available

C-terminal modification: Linear

N-terminal modification : TAT

Non-natural peptide information: Dansylglycine = fluorescent amino acid residue located in the side chain of lysine

Assay type : MTT assay

Assay time : 24-h

Activity : IC50 = 11.1 ± 0.1 μM

Cell line : A-375

Cancer type : Skin Cancer

Other activity : Anticancer

Amino Acid Composition Bar Chart : Not available

Molecular mass : Not available

Aliphatic index : Not available

Instability index : Not available

Hydrophobicity (GRAVY) : Not available

Isoelectric point : Not available

Charge (pH 7) : Not available

Aromaticity : Not available

Molar extinction coefficient (cysteine, cystine): Not available

Hydrophobic/hydrophilic ratio : Not available

hydrophobic moment : Not available

Missing amino acid : Not available

Most occurring amino acid : Not available

Most occurring amino acid frequency : Not available

Least occurring amino acid : Not available

Least occurring amino acid frequency : Not available

3D-structure: Not available

Secondary structure fraction (Helix, Turn, Sheet): Not available

SMILES Notation: Not available

Molecular descriptors: Not available

ADMET properties: Not available

1 : Zhang F, et al. Mitochondrial Voltage-Dependent Anion Channel 1-Hexokinase-II Complex-Targeted Strategy for Melanoma Inhibition Using Designed Multiblock Peptide Amphiphiles. ACS Appl Mater Interfaces. 2021; 13:35281-35293. doi: 10.1021/acsami.1c04385

Paper title : Mitochondrial Voltage-Dependent Anion Channel 1-Hexokinase-II Complex-Targeted Strategy for Melanoma Inhibition Using Designed Multiblock Peptide Amphiphiles.

Doi : https://doi.org/10.1021/acsami.1c04385

Abstract : Targeted therapies of melanoma are of urgent need considering the resistance of this aggressive type of cancer to chemotherapeutics. The voltage-dependent anion channel 1 (VDAC1)-hexokinase-II (HK-II) complex is an emerging target for novel anticancer therapies based on induced mitochondria-mediated apoptosis. The low cell membrane permeability of the anticancer 12-mer peptide N-Ter (RDVFTKGYGFGL) derived from the N-terminal fragment of the VDAC1 protein impedes the intracellular targeting. Here, novel multiblock VDAC1-derived cationic amphiphilic peptides (referred to as Pal-N-Ter-TAT, pFL-N-Ter-TAT, and Pal-pFL-N-Ter-TAT) are designed with a self-assembly propensity and cell-penetrating properties. The created multiblock amphiphilic peptides of partial α-helical conformations form nanoparticles of ellipsoid-like shapes and are characterized by enhanced cellular uptake. The amphiphilic peptides can target mitochondria and dissociate the VDAC1-HK-II complex at the outer mitochondrial membrane, which result in mitochondria-mediated apoptosis. The latter is associated with decrease of the mitochondrial membrane potential, cytochrome c release, and changes of the expression levels of the apoptotic proteins in A375 melanoma cells. Importantly, the mitochondrial VDAC1-derived amphiphilic peptides have a comparable IC₅₀ value for melanoma cells to a small-molecule drug, sorafenib, which has been previously used in clinical trials for melanoma. These results demonstrate the potential of the designed peptide constructs for efficient melanoma inhibition.