Peptide name : MIPP

Source/Organism : Plant sources

Linear/Cyclic : Linear

Chirality : L

Peptide length: 8

C-terminal modification: Linear

N-terminal modification : Not found

Non-natural peptide information: None

Assay type : SRB assay

Assay time : 1h

Activity : Not found

Cell line : HeLa

Cancer type : Human endometrial cancer

Other activity : Not found

Amino acid composition bar chart :

Molecular mass : 831.957 Dalton

Aliphatic index : 1.462

Instability index : 8.75

Hydrophobicity (GRAVY) : 0.8375

Isoelectric point : 9.4651

Charge (pH 7) : 0.4601

Aromaticity : 0

Molar extinction coefficient (cysteine, cystine): (0, 0)

Hydrophobic/hydrophilic ratio : 1

hydrophobic moment : -0.970

Missing amino acid : C,W,H,Q,T,P,M,I,E,K,F,D,Y,N,G

Most occurring amino acid : S

Most occurring amino acid frequency : 3

Least occurring amino acid : V

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (0.3, 0.3, 0.3)

SMILES Notation: CC(C)C[C@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)C(C)C

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.